Myelodysplastic syndrome
Encyclopedia
The myelodysplastic syndromes (MDS, formerly known as preleukemia) are a diverse collection of hematological
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...

 (blood-related) medical conditions that involve ineffective production (or dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...

) of the myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...

 class of blood cells.

Patients with MDS often develop severe anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

 and require frequent blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

s. In most cases, the disease worsens and the patient develops cytopenia
Cytopenia
Cytopenia is a reduction in the number of blood cells. It takes a number of forms:*Low red blood cell count: resulting in anemia.*Low white blood cell count: leukopenia or neutropenia .*Low platelet count: thrombocytopenia.*Low granulocyte count: granulocytopenia*Low red blood...

s (low blood counts) due to progressive bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 failure. In about one third of patients with MDS, the disease transforms
Malignant transformation
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as malignant degeneration of a previously existing benign tumor....

 into acute myelogenous leukemia (AML), usually within months to a few years.

The myelodysplastic syndromes are all disorders of the stem cell in the bone marrow. In MDS, hematopoiesis (blood production) is disorderly and ineffective. The number and quality of blood-forming cells decline irreversibly, further impairing blood production.

French-American-British (FAB) classification

In 1974 and 1975, a group of pathologists from France, the US, and Britain produced the first widely used classification of these diseases. This French-American-British classification
French-American-British classification
The French-American-British classification systems refers to a series of classifications of hematologic diseases.It was first produced in 1976.Types include:* FAB classification of acute lymphoblastic leukemias...

 was published in 1976, and revised in 1982. Cases were classified into five categories: (ICD-O codes are provided where available)
ICD-O Name Description
Refractory anemia (RA) characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors
Refractory anemia with ringed sideroblasts (RARS) also characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts"
Refractory anemia with excess blasts (RAEB) characterized by 5-20% myeloblasts in the marrow
Refractory anemia with excess blasts in transformation (RAEB-T) characterized by 21-30% myeloblasts in the marrow (>30% blasts is defined as acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...

)
Chronic myelomonocytic leukemia
Chronic myelomonocytic leukemia
Chronic myelomonocytic leukemia is a form of leukemia featuring monocytosis.The categorization of this disease has been controversial. Patients with CMML can present with various clinical features, mimicking either myelodysplastic syndroms or myeloproliferative neoplasms depending upon a patient's...

(CMML), not to be confused with chronic myelogenous leukemia
Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...

 or CML
characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 * 109/uL monocytes (a type of white blood cell) circulating in the peripheral blood.


A table comparing these is available from the Cleveland Clinic.

The best prognosis is seen with refractory anemia with ringed sideroblasts and refractory anemia, where some non-transplant patients live more than a decade (the average is on the order of three to five years, although long-term remission is possible if a bone marrow transplant is successful). The worst outlook is with RAEB-T, where the mean life expectancy is less than 1 year. About one quarter of patients develop overt leukemia. The others die of complications of low blood count or unrelated disease. The International Prognostic Scoring System is another tool for determining the prognosis of MDS, published in Blood in 1997. This system takes into account the percentage of blasts in the marrow, cytogenetics, and number of cytopenias.

The FAB classification was used by pathologists and clinicians for almost 20 years.

World Health Organization

In the late 1990s a group of pathologists and clinicians working under the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) modified this classification, introducing several new disease categories and eliminating others. Most recently the WHO has evolved a new classification scheme (2008) which is based more on genetic findings. However, morphology of the cells in the peripheral blood, bone marrow aspirate, and bone marrow biopsy is still the screening test used in order to decide which classification is best and which cytogenetic aberrations may be related.

The list of dysplastic syndromes under the new WHO system includes:
Old system New system
Refractory anemia (RA) Refractory cytopenia
Cytopenia
Cytopenia is a reduction in the number of blood cells. It takes a number of forms:*Low red blood cell count: resulting in anemia.*Low white blood cell count: leukopenia or neutropenia .*Low platelet count: thrombocytopenia.*Low granulocyte count: granulocytopenia*Low red blood...

 with unilineage dysplasia (Refractory anemia, Refractory neutropenia, and Refractory thrombocytopenia)
Refractory anemia with ringed sideroblasts (RARS) Refractory anemia with ring sideroblasts (RARS)

Refractory anemia with ring sideroblasts - thrombocytosis (RARS-t) (provisional entity) which is in essence a myelodysplastic/myeloproliferative disorder and usually has a JAK2 mutation (janus kinase) - New WHO classification 2008
Refractory cytopenia with multilineage dysplasia
Refractory cytopenia with multilineage dysplasia
Refractory cytopenia with multilineage dysplasia is a form of myelodysplastic syndrome.It is abbreviated "RCMD"....

 (RCMD) includes the subset Refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). RCMD includes patients with pathological changes not restricted to red cells (i.e., prominent white cell precursor and platelet precursor (megakaryocyte) dysplasia.
Refractory anemia with excess blasts (RAEB) Refractory anemia with excess blasts I and II. RAEB was divided into *RAEB-I (5-9% blasts) and RAEB-II (10-19%) blasts, which has a poorer prognosis than RAEB-I. Auer rods
Auer rods
Auer rods can be seen in the leukemic blasts of acute myeloid leukemia. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts...

 may be seen in RAEB-II which may be difficult to distinguish from acute myeloid leukemia.
Refractory anemia with excess blasts in transformation (RAEB-T) The category of RAEB-T was eliminated; such patients are now considered to have acute leukemia. 5q- syndrome, typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells, was added to the classification.
Chronic myelomonocytic leukemia
Chronic myelomonocytic leukemia
Chronic myelomonocytic leukemia is a form of leukemia featuring monocytosis.The categorization of this disease has been controversial. Patients with CMML can present with various clinical features, mimicking either myelodysplastic syndroms or myeloproliferative neoplasms depending upon a patient's...

(CMML)
CMML was removed from the myelodysplastic syndromes and put in a new category of myelodysplastic-myeloproliferative overlap syndromes.
5q- syndrome
5q- syndrome
Chromosome 5q deletion syndrome is a rare disorder caused by loss of part of the long arm of human chromosome 5....

Myelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosis and others)
Refractory cytopenia of childhood (dysplasia in childhood) - New WHO classification 2008


Not all physicians concur with this reclassification. This is because the underlying pathology of the diseases is not well understood. It is difficult to classify things that are not well understood.

Myelodysplastic syndrome unclassified

WHO proposed criteria for diagnosis and classification of MDS apply to most cases. However, occasional cases are difficult to classify into defined categories because of one or more unusual features:
I- Rare cases with less than 5% blast will present with auer rods. These cases usually have the features of RAMD.
II- Occasionally cases of MDS present with isolated neutropenia or thrombocytopenia without anemia and with dysplastic changes confined to the single lineage. The term refractory neutropenia and refractory thrombocytopenia have sometimes used to describe these cases. A diagnosis of MDS in patients with neutropenia or thromobocytopenia without anemia should be made with caution.
III- Patients with RA or RAEB occasionally present with leukocytosis or thrombocytosis instead of usual cytopenia.

Signs and symptoms

The median age at diagnosis of a MDS is between 60 and 75 years; a few patients are younger than 50; MDS diagnoses are rare in children. Males are slightly more commonly affected than females. Signs and symptoms are nonspecific and generally related to the blood cytopenias:
  • Anemia
    Anemia
    Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

    —chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain
  • Neutropenia
    Neutropenia
    Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...

     (low neutrophil count) —increased susceptibility to infection
    Infection
    An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

  • Thrombocytopenia
    Thrombocytopenia
    Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

     (low platelet count) —increased susceptibility to bleeding
    Bleeding
    Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

     and ecchymosis
    Ecchymosis
    An ecchymosis is the medical term for a subcutaneous purpura larger than 1 centimeter or a hematoma, commonly called a bruise. It can be located in the skin or in a mucous membrane.-Presentation:...

     (bruising), as well as subcutaneous hemorrhaging resulting in purpura
    Purpura
    Purpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure. They are caused by bleeding underneath the skin...

     or petechia
    Petechia
    A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...



Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:
  • neutropenia
    Neutropenia
    Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...

    , anemia
    Anemia
    Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

     and thrombocytopenia
    Thrombocytopenia
    Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

     (low cell counts of white and red blood cells, and platelets, respectively);
  • splenomegaly
    Splenomegaly
    Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...

     or rarely hepatomegaly
    Hepatomegaly
    Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

    ;
  • abnormal granules in cells, abnormal nuclear shape and size; and/or
  • chromosomal
    Chromosome
    A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

     abnormalities, including chromosomal translocation
    Chromosomal translocation
    In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...

    s and abnormal chromosome number.


Although there is some risk for developing acute myelogenous leukemia, about 50% of deaths occur as a result of bleeding or infection. Leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment.

Pathophysiology

MDS is caused by environmental exposures such as radiation and benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....

; other risk factors have been reported inconsistently. Secondary MDS occurs as a late toxicity of cancer treatment, usually with a combination of radiation and the radiomimetic alkylating agents such as busulfan
Busulfan
Busulfan is a cancer drug, in use since 1959.Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates...

, nitrosourea, or procarbazine
Procarbazine
Procarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It...

 (with a latent period of 5 to 7 years) or the DNA topoisomerase inhibitors (2 years). Both acquired aplastic anemia following immunosuppressive treatment and Fanconi's anemia can evolve into MDS.

MDS is thought to arise from mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

s in the multi-potent bone marrow stem cell, but the specific defects responsible for these diseases remain poorly understood. Differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

 of blood precursor cells is impaired, and there is a significant increase in levels of apoptotic
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 cell death in bone marrow cells. Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate. If the overall percentage of bone marrow blasts rises over a particular cutoff (20% for WHO and 30% for FAB) then transformation to acute myelogenous leukemia (AML) is said to have occurred. The progression of MDS to AML is a good example of the multi-step theory of carcinogenesis
Knudson hypothesis
The Knudson hypothesis is the hypothesis that cancer is the result of accumulated mutations to a cell's DNA. It was first proposed by Carl O. Nordling in 1953, and later formulated by Alfred G. Knudson in 1971. Knudson's work led indirectly to the identification of cancer-related genes...

in which a series of mutations occur in an initially normal cell and transform it into a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 cell.

While recognition of leukemic transformation was historically important (see History), a significant proportion of the morbidity and mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 attributable to MDS results not from transformation to AML but rather from the cytopenias seen in all MDS patients. While anemia is the most common cytopenia
Cytopenia
Cytopenia is a reduction in the number of blood cells. It takes a number of forms:*Low red blood cell count: resulting in anemia.*Low white blood cell count: leukopenia or neutropenia .*Low platelet count: thrombocytopenia.*Low granulocyte count: granulocytopenia*Low red blood...

 in MDS patients, given the ready availability of blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

 MDS patients rarely suffer injury from severe anemia. However, if an MDS patient is fortunate enough to suffer nothing more than anemia over several years, they then risk iron overload. The two most serious complications in MDS patients resulting from their cytopenia
Cytopenia
Cytopenia is a reduction in the number of blood cells. It takes a number of forms:*Low red blood cell count: resulting in anemia.*Low white blood cell count: leukopenia or neutropenia .*Low platelet count: thrombocytopenia.*Low granulocyte count: granulocytopenia*Low red blood...

s are bleeding (due to lack of platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days...

s) or infection (due to lack of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

s). Long-term, transfusion of packed red blood cells
Packed red blood cells
In transfusion medicine, packed red blood cells are red blood cells that have been separated from whole blood for transfusion purposes. The product is typically abbreviated RBC or PRBC, and sometimes LRBC for leukoreduced products...

 leads to iron overload.

The recognition of epigenetic changes in DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 structure in MDS has explained the success of two of three commercially available medications approved by the U.S. Food and Drug Administration (FDA) to treat MDS. Proper DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...

 is critical in the regulation of proliferation genes, and the loss of DNA methylation control can lead to uncontrolled cell growth, and cytopenias. The recently approved DNA methyltransferase inhibitors take advantage of this mechanism by creating a more orderly DNA methylation profile in the hematopoietic stem cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

, and thereby restore normal blood counts and retard the progression of MDS to acute leukemia
Acute leukemia
Acute leukemia or acute leukaemia is a generic term used to describe a family of serious medical conditions relating to an original diagnosis of leukemia...

.

Some authors have proposed that the loss of mitochondrial function over time leads to the accumulation of DNA mutations in hematopoietic stem cells, and this accounts for the increased incidence of MDS in older patients. Researchers point to the accumulation of mitochondrial iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 deposits in the ringed sideroblast as evidence of mitochondrial dysfunction in MDS.

5q- syndrome

Since at least 1974, the loss of the long arm of chromosome 5 has been associated with dysplastic abnormalities of hematopoietic stem cells. By 2005, it was recognized that Lenalidomide
Lenalidomide
Lenalidomide , initially known as CC-5013 and marketed as Revlimid by Celgene, is a derivative of thalidomide introduced in 2004....

 was effective in MDS patients with the 5q- syndrome
5q- syndrome
Chromosome 5q deletion syndrome is a rare disorder caused by loss of part of the long arm of human chromosome 5....

, and in December 2005, the US FDA approved the drug for this indication.

Diagnosis

MDS must be differentiated
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 from anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

, and/or leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....

. Usually, the elimination of other causes of these cytopenias, along with a dysplastic bone marrow, is required to diagnose a myelodysplastic syndrome.
A typical investigation includes:
  • Full blood count and examination of blood film
    Blood film
    A blood film or peripheral blood smear is a thin layer of blood smeared on a microscope slide and then stained in such a way to allow the various blood cells to be examined microscopically...

    . The blood film morphology can provide clues about hemolytic anemia
    Hemolytic anemia
    Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...

    , clumping of the platelets leading to spurious thrombocytopenia
    Thrombocytopenia
    Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

    , or leukemia
    Leukemia
    Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

    .
  • Blood tests to eliminate other common causes of cytopenias, such as lupus
    Lupus erythematosus
    Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...

    , hepatitis
    Hepatitis
    Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

    , B12
    Vitamin B12
    Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

    , folate, or other vitamin
    Vitamin
    A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

     deficiencies, renal failure
    Renal failure
    Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

     or heart failure, HIV
    HIV
    Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

    , hemolytic anemia
    Hemolytic anemia
    Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...

    , monoclonal gammopathy
    Monoclonal gammopathy
    Monoclonal gammopathy is a synonym for paraproteinemia.- External links :*...

    . Age-appropriate cancer screening
    Cancer screening
    Cancer screening aims to detect cancer before symptoms appear. This may involve blood tests, urine tests, other tests, or medical imaging. The benefits of screening in terms of cancer prevention, early detection and subsequent treatment must be weighed against any harms.Universal screening, mass...

     should be considered for all anemic patients.
  • Bone marrow examination by a hematopathologist. This is required to establish the diagnosis, since all hematopathologists consider dysplastic marrow the key feature of myelodysplasia.
  • Cytogenetics
    Cytogenetics
    Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...

     or chromosomal studies. This is ideally performed on the bone marrow aspirate. Conventional cytogenetics requires a fresh specimen, since live cells are induced to enter metaphase
    Metaphase
    Metaphase, from the ancient Greek μετά and φάσις , is a stage of mitosis in the eukaryotic cell cycle in which condensed & highly coiled chromosomes, carrying genetic information, align in the middle of the cell before being separated into each of the two daughter cells...

     to enhance chromosomal staining. Alternatively, virtual karyotyping
    Virtual Karyotype
    Virtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...

     can be done for MDS, which uses computational tools to construct the karyogram from disrupted DNA. Virtual karyotyping does not require cell culture and has dramatically higher resolution than conventional cytogenetics, but cannot detect balanced translocations.
  • Flow cytometry
    Flow cytometry
    Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

     is helpful to establish the presence of any lymphoproliferative disorder in the marrow.


Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...

, and pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important historic fact. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process. Children with Down syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...

 are susceptible to MDS, and a family history may indicate a hereditary form of sideroblastic anemia
Sideroblastic anemia
Sideroblastic anemia or sideroachrestic anemia is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells . It may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can evolve into hematological malignancies...

 or Fanconi anemia
Fanconi anemia
Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...

.

The average age at diagnosis for MDS is about 65 years, but pediatric cases have been reported. Some patients have a history of exposure to chemotherapy (especially alkylating agents such as melphalan
Melphalan
Melphalan hydrochloride is a chemotherapy drug belonging to the class of nitrogen mustard alkylating agents.An alkylating agent adds an alkyl group to DNA...

, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

, busulfan
Busulfan
Busulfan is a cancer drug, in use since 1959.Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates...

, and chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...

) or radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...

 (therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease). Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population. Males are slightly more frequently affected than females. Xylene
Xylene
Xylene encompasses three isomers of dimethylbenzene. The isomers are distinguished by the designations ortho- , meta- , and para- , which specify to which carbon atoms the two methyl groups are attached...

 and benzene exposure has been associated with myelodysplasia. Vietnam veteran
Vietnam veteran
Vietnam veteran is a phrase used to describe someone who served in the armed forces of participating countries during the Vietnam War.The term has been used to describe veterans who were in the armed forces of South Vietnam, the United States armed forces, and countries allied to them, whether or...

s that were exposed to Agent Orange
Agent Orange
Agent Orange is the code name for one of the herbicides and defoliants used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. Vietnam estimates 400,000 people were killed or maimed, and 500,000 children born with birth...

 are at risk of developing MDS.

The features generally used to define a MDS are: blood cytopenias; ineffective hematopoiesis; dyserythropoiesis; dysgranulopoiesis; dysmegakaropoiesis and increased myeloblast.

Dysplasia can affect all three lineages seen in the bone marrow. The best way to diagnose dysplasia is by morphology and special stains (PAS) used on the bone marrow aspirate and peripheral blood smear. Dysplasia in the myeloid series is defined by:
  • Granulocytic series
    1. Hypersegmented neutrophils (also seen in Vit B12/Folate deficiency)
    2. Hyposegmented neutrophils (Pseudo-Pelger Huet)
    3. Hypogranular neutrophils or pseudo Chediak Higashi large granules
    4. Auer rods - automatically RAEB II (if blast count <5% in the peripheral blood and <10% in the bone marrow aspirate) also note Auer rods may be seen in mature neutrophils in AML with translocation t(8;21)
    5. Dimorphic granules (basophilic and eosinophilic granules) within eosinophils
  • Erythroid series
    1. Binucleated erythroid percursors and karyorrhexis
    2. Erythroid nuclear budding
    3. Erythroid nuclear strings or internuclear bridging (also seen in congenital dyserythropoietic anemias)
    4. Loss of E-cadherin in normoblasts is a sign of aberrancy
    5. PAS (globular in vacuoles or diffuse cytoplasmic staining) within erythroid precursors in the bone marrow aspirate (has no bearing on paraffin fixed bone marrow biopsy). Note: One can see PAS vacuolar positivity in L1 and L2 blasts (AFB classification; the L1 and L2 nomenclature is not used in the WHO classification)
    6. Ringed sideroblasts seen on Prussian blue iron stain (10 or more iron granules encircling 1/3 or more of the nucleus and >15% ringed sideroblasts when counted amongst red cell precursors)
  • Megakaryocytic series (can be the most subjective)
    1. Hyposegmented nuclear features in platelet producing megakaryocytes (lack of lobation)
    2. Hypersegmented (osteoclastic appearing) megakaryocytes
    3. Ballooning of the platelets (seen with interference contrast microscopy)


Other stains can help in special cases (PAS and napthol ASD chloroacetate esterase positivity) in eosinophils is a marker of abnormality seen in chronic eosinophilic leukemia and is a sign of aberrancy.

On the bone marrow biopsy high grade dysplasia (RAEB-I and RAEB-II) may show atypical localization of immature precursors (ALIPs) which are islands of immature precursors cells (myeloblasts and promyelcytes) localized to the center of intertrabecular space rather than adjacent to the trabeculae or surrounding arterioles. This morphology can be difficult to recognize from treated leukemia and recovering immature normal marrow elements. Also topographic alteration of the nucleated erythroid cells can be seen in early myelodysplasia (RA and RARS), where normoblasts are seen next to bony trabeculae instead of forming normal interstitially placed erythroid islands.

Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores, vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...

 deficiencies, and nutrient deficiencies are ruled out. Also congenital diseases such as congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells in the body and a less than normal quantity of hemoglobin in...

 (CDA I through IV) has been recognized, Pearson's syndrome (sideroblastic anemia)
Sideroblastic anemia
Sideroblastic anemia or sideroachrestic anemia is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells . It may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can evolve into hematological malignancies...

, Jordans anomaly - vacuolization in all cell lines may be seen in Chanarin-Dorfman syndrome, ALA (aminolevulinic acid) enzyme deficiency, and other more esoteric enzyme deficiencies are known to give a pseudomyelodysplastic picture in one of the cell lines, however, all three cell lines are never morphologically dysplastic in these entities with the exception of chloramphenicol, arsenic toxicity and other poisons.

All of these conditions are characterized by abnormalities in the production of one or more of the cellular components of blood (red cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

s, white cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

s other than lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

s and platelets or their progenitor cells, megakaryocyte
Megakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...

s).

Management

The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to acute myelogenous leukemia (AML).

The IPSS scoring system can help triage
Triage
Triage or ) is the process of determining the priority of patients' treatments based on the severity of their condition. This rations patient treatment efficiently when resources are insufficient for all to be treated immediately. The term comes from the French verb trier, meaning to separate,...

 patients for more aggressive treatment (i.e. bone marrow transplant
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...

) as well as help determine the best timing of this therapy. Supportive care with blood product support and hematopoeitic growth factors (e.g. erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...

) is the mainstay of therapy. The regulatory environment for the use of erythropoietins is evolving, according to a recent US Medicare
Medicare (United States)
Medicare is a social insurance program administered by the United States government, providing health insurance coverage to people who are aged 65 and over; to those who are under 65 and are permanently physically disabled or who have a congenital physical disability; or to those who meet other...

 National Coverage Determination
National coverage determination
A national coverage determination is a nationwide determination of whether Medicare will pay for an item or service. For more information see http://www.cms.hhs.gov/mcd/overview.asp....

. No comment on the use of hematopoeitic growth factors for MDS was made in that document.

Three agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of MDS:
  1. 5-azacytidine
    5-Azacytidine
    Azacitidine or 5-azacytidine, sold under the trade name Vidaza, is a chemical analogue of cytidine, a nucleoside present in DNA and RNA. Azacitidine and its deoxy derivative, decitabine , are used in the treatment of myelodysplastic syndrome...

    : 21 month median survival
  2. Decitabine: Complete response rate reported as high as 43%. A phase I study has shown efficacy in AML when decitabine is combined with valproic acid
    Valproic acid
    Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...

    .
  3. Lenalidomide
    Lenalidomide
    Lenalidomide , initially known as CC-5013 and marketed as Revlimid by Celgene, is a derivative of thalidomide introduced in 2004....

    : Effective in reducing red blood cell transfusion requirement in patients with the chromosome 5q deletion subtype of MDS


Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 with the hypomethylating agents
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...

 5-azacytidine and decitabine has been shown to decrease blood transfusion requirements and to retard the progression of MDS to AML. Lenalidomide was approved by the FDA in December 2005 only for use in the 5q- syndrome
5q- syndrome
Chromosome 5q deletion syndrome is a rare disorder caused by loss of part of the long arm of human chromosome 5....

. In the United States, treatment of MDS with lenalidomide costs about US$9,200 per month.

Stem cell transplantation, particularly in younger patients (i.e. less than 40 years of age), more severely affected patients, offers the potential for curative therapy. Success of bone marrow transplantation has been found to correlate with severity of MDS as determined by the IPSS score, with patients having a more favorable IPSS score tending to have a more favorable outcome with transplantation.

Iron overload in MDS, red blood cell (RBC) transfusions are a major part of the supportive care for anemic MDS patients. Although the specific therapies patients receive may alleviate the RBC transfusion need, many MDS patients may not respond to these treatments and may develop iron overload as well as its consequences.

Patients requiring relatively large numbers of RBC transfusions have experienced adverse effect of chronic iron overload on liver, heart, endocrine functions. It is possible that this organ disfunction may result from iron overload in patients with MDS and that transfusional iron overload might be a contributor to increased sickness and death in early stage MDS.

For patients requiring many RBC transfusions, serum ferritin levels, number of RBC transfusions received, and associated organ dysfunction (heart, liver, and pancreas) should be monitored to determine iron levels. Monitoring serum ferritin may also be useful, aiming to decrease ferritin levels to <1000 mcg/L.

There are currently two iron chelators
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....

 available in the US, deferoxamine
Deferoxamine
Deferoxamine is a bacterial siderophore produced by the actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body...

 (Desferal) for IV use and deferasirox
Deferasirox
Deferasirox is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias...

 (Exjade) for oral use. These options now provide potentially useful drugs for treating this iron overload problem. A third chelating agent is available in Europe, deferiprone
Deferiprone
Deferiprone is an oral drug that chelates iron and is used to treat thalassaemia major.It has been licensed for use in Europe and Asia for many years while awaiting approval in Canada and the United States. On October 14, 2011, however, "the U.S...

 for oral use, but not available in the US.

Clinical trials in the MDS are ongoing with iron chelating agents to address the question of whether iron chelation alters the natural history of patients with MDS who are transfusion dependent. Reversal of some of the consequences of iron overload in MDS by iron chelation therapy have been shown.

Both the MDS Foundation and the NCCN MDS Guidelines Panel have recommended that chelation therapy be considered to decrease iron overload in selected MDS patients. Evidence also suggest there is a potential value to iron chelation in patients who then undergo a stem cell transplant.

Although deferasirox is generally well tolerated (other than episodes of gastrointestinal distress and kidney dysfunction in some patients), recently a safety warning by the FDA and Novartis was added to deferasirox treatment guidelines. Following post-marketing use of deferasirox, there were rare cases of acute kidney failure or liver failure, some resulting in death. Due to this, it is recommended that patients be closely monitored on deferasirox therapy prior to the start of therapy and regularly thereafter.

Currently, a large international Phase III clinical trial is ongoing comparing treatment of deferasirox to placebo, which should help to establish the clinical value of deferasirox in iron- overloaded MDS patients.

Prognosis

Indicators of a good prognosis
Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow(<20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal karyotypes of mixed karyotypes without complex chromosome abnormalities and in vitro marrow culture- non leukemic growth pattern.

Indicators of a poor prognosis
Advanced age; Severe neutropenia or thrombocytopenia ; high blast count in the bone marrow (20-29%) or blasts in the blood;
Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section
all or mostly abnormal karyotypes or complex marrow chromosome abnormalities and in vitro bone emarrow culture-leukemic growth pattern.

Prognosis and karyotype
Good: Normal, -Y, del(5q), del(20q)

Intermediate or variable: +8, other single or double anomalies

Poor; Complex (>3 chromosomal aberrations); chromosome 7 anomalies

The International Prognostic Scoring System
International Prognostic Scoring System
The International Prognostic Scoring System is used by many doctors to help assess the severity of a patient's myelodysplastic syndrome...

 (IPSS) is the most commonly used tool in MDS to predict long-term outcome.

Cytogenetic abnormalities can be detected by conventional cytogenetics, a FISH panel for MDS, or Virtual Karyotype
Virtual Karyotype
Virtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...

.

Epidemiology

The exact number of people with MDS is not known because it can go undiagnosed and there is no mandated tracking of the syndrome. Some estimates are on the order of 10,000 to 20,000 new cases each year in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 alone. The incidence is probably increasing as the age of the population increases, and some authors propose that the incidence in patients over 70 may be as high as 15 cases per 100,000 per year.

History

Since the early 20th century it began to be recognized that some people with acute myelogenous leukemia had a preceding period of anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

 and abnormal blood cell
Blood cell
A blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...

 production. These conditions were lumped with other diseases under the term "refractory anemia". The first description of "preleukemia" as a specific entity was published in 1953 by Block et al. The early identification, characterization and classification of this disorder were problematical, and the syndrome went by many names until the 1976 FAB classification was published and popularized the term MDS.

Famous patients

Famous patients with MDS include astronomer Carl Sagan
Carl Sagan
Carl Edward Sagan was an American astronomer, astrophysicist, cosmologist, author, science popularizer and science communicator in astronomy and natural sciences. He published more than 600 scientific papers and articles and was author, co-author or editor of more than 20 books...

, writer Roald Dahl
Roald Dahl
Roald Dahl was a British novelist, short story writer, fighter pilot and screenwriter.Born in Wales to Norwegian parents, he served in the Royal Air Force during the Second World War, in which he became a flying ace and intelligence agent, rising to the rank of Wing Commander...

, jazz musicians Michael Brecker
Michael Brecker
Michael Leonard Brecker was an American jazz saxophonist and composer. Acknowledged as "a quiet, gentle musician widely regarded as the most influential tenor saxophonist since John Coltrane," he has been awarded 15 Grammy Awards as both performer and composer and was inducted into Down Beat Jazz...

 and Paul Motian
Paul Motian
Stephen Paul Motian was an American jazz drummer, percussionist and composer of Armenian extraction.He first came to prominence in the late 1950s in the piano trio of Bill Evans, and later led several groups...

, actress Nina Foch
Nina Foch
Nina Foch was a Dutch-born American actress and leading lady in many 1940s and 1950s films.- Personal life :...

, firearms executive Val Forgett
Val Forgett
Val J. Forgett, Jr., Founder of Navy Arms Company, Inc. and internationally recognized as the "father of the modern replica firearms business". Forgett created over 100 different replica firearms models in his lifetime...

, United States Congressmen
United States Congress
The United States Congress is the bicameral legislature of the federal government of the United States, consisting of the Senate and the House of Representatives. The Congress meets in the United States Capitol in Washington, D.C....

 Joe Moakley
Joe Moakley
John Joseph "Joe" Moakley was a Democratic congressman from the Ninth District of Massachusetts, a seat held two years earlier by Speaker John William McCormack. Moakley was the last chairman of the U.S...

 and Bob Matsui
Bob Matsui
Robert Takeo Matsui was an American politician from the state of California. Matsui was a member of the Democratic Party and served in the U.S...

, actor Pat Hingle
Pat Hingle
Martin Patterson "Pat" Hingle was an American actor.-Early life:Hingle was born Martin Patterson Hingle in Miami, Florida, the son of Marvin Louise , a schoolteacher and musician, and Clarence Martin Hingle, a building contractor. Hingle enlisted in the U.S. Navy in December 1941, dropping out of...

, singer and comedienne Fran Allison
Fran Allison
Fran Allison was an American television and radio comedian, personality and singer. She is best known for her starring role on the weekday NBC-TV puppet show Kukla, Fran and Ollie, which ran from 1947 to 1957, occasionally returning to the air until the mid 1980s...

, Holocaust survivor Henry Kucharski, radio personality J.P. McCarthy, Danish theoretical physicist Per Bak
Per Bak
Per Bak was a Danish theoretical physicist who coauthored the 1987 academic paper that coined the term "self-organized criticality."- Life and work :...

, and pioneering plant pathologist Jack Bailey
North Carolina State University College of Agriculture and Life Sciences
North Carolina State University's College of Agriculture and Life Sciences is the second largest college in the university and one of the largest colleges of its kind in the nation, with nearly 6,000 students pursuing associate, bachelor’s, master’s and doctoral degrees and more than 1,600...

.

External links


Online Medical Reference

See also

  • Myeloproliferative syndrome
  • Acute myeloid leukemia
    Acute myeloid leukemia
    Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...

  • Chloroma
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