Myeloproliferative disease
Encyclopedia
The myeloproliferative diseases (MPDs, myeloproliferative neoplasms, MPNs) are a group of diseases of the bone marrow
in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome
and acute myeloid leukemia
, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the eminent hematologist William Dameshek
. In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.
like other cancers, MPDs are classified within the hematological neoplasms
.
There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome
:
In 2001, the World Health Organization
classified "chronic eosinophilic leukemia
/ hypereosinophilic syndrome
" and chronic neutrophilic leukemia
under "Chronic myeloproliferative diseases".
lineage in the bone marrow. The lymphoid lineage may produce similar diseases, the lymphoproliferative disorders (acute lymphoblastic leukemia
, lymphoma
s, chronic lymphocytic leukemia
and multiple myeloma
).
According to the WHO Classification of Hematopoietic and Lymphoid Neoplasms 2008 myeloproliferative disorders are divided into the following by diagnostic characteristics:
a. u-BCR-ABL (p230): leads to CML with usual neutrophilia and basophilia
b. minor-BCR-ABL (p190): leads to CML which has a tendency to become acute lymphoblastic leukemia (ALL) usually precursor B ALL and rarely precursor T ALL
c. major-BCR-ABL (p210): normal usual breakpoint
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome (collagenous) fibrosis, and increased myeloid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome fibrosis, and increased myeloid and erythroid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
a. Cellular phase - increased large megakaryocytes with fibrosis and little increase in other bone marrow elements
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
These disorders are still being revised according to more specific genetic mutations and how often patients end in a fibrotic marrow event.
In 2005, the discovery of the JAK2 V617F mutation provided some evidence to suggest a common pathogenesis for the Philadelphia Chromosome negative MPDs.
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...
in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
and 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...
, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the eminent hematologist William Dameshek
William Dameshek
William Dameshek was an American hematologist. Trained at Harvard, he was the founder of Blood, the prime core clinical journal of hematology, in 1946. He is also credited with describing the concept of myeloproliferative diseases in 1951...
. In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.
Classification
Although not a malignant neoplasmCancer
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...
like other cancers, MPDs are classified within the hematological neoplasms
Hematological malignancy
Hematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
.
There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome
Philadelphia chromosome
Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
:
| Philadelphia Chromosome "positive" | Philadelphia Chromosome "negative" |
|---|---|
|
Polycythemia vera Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the... (PV) Essential thrombocytosis Essential thrombocythemia is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis... (ET) Myelofibrosis Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow... (MF) |
In 2001, 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...
classified "chronic eosinophilic leukemia
Chronic eosinophilic leukemia
Chronic eosinophilic leukemia is a disease in which too many eosinophils are found in the bone marrow, blood, and other tissues. CEL may stay the same for many years, or it may progress quickly to acute leukemia. It is generally caused by overactivation of the oncogene PDGFRA through a chromosome...
/ hypereosinophilic syndrome
Hypereosinophilic syndrome
The hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.HES is a diagnosis of exclusion, after clonal...
" and chronic neutrophilic leukemia
Chronic neutrophilic leukemia
Chronic neutrophilic leukemia is a rare myeloproliferative disorder that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.-Epidemiology:This is a rare disease,...
under "Chronic myeloproliferative diseases".
Causes
All MPDs arise from precursors of the myeloidMyeloid
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...
lineage in the bone marrow. The lymphoid lineage may produce similar diseases, the lymphoproliferative disorders (acute lymphoblastic leukemia
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone...
, lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s, chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
and multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
).
Diagnosis
Depending on the nature of the myeloproliferative disorder, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B12 (or B12 binding capacity) and serum urate.According to the WHO Classification of Hematopoietic and Lymphoid Neoplasms 2008 myeloproliferative disorders are divided into the following by diagnostic characteristics:
1. Chronic myelogenous leukemia (CML)
with defining translocation t(9;22) BCR-ABL translocation which has three breakpoints:a. u-BCR-ABL (p230): leads to CML with usual neutrophilia and basophilia
b. minor-BCR-ABL (p190): leads to CML which has a tendency to become acute lymphoblastic leukemia (ALL) usually precursor B ALL and rarely precursor T ALL
c. major-BCR-ABL (p210): normal usual breakpoint
2. Primary myelofibrosis
associated with JAK2 mutation in up to 50% of cases and MPL (thrombopoietin receptor) mutation in up to 5% of cases:a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome (collagenous) fibrosis, and increased myeloid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
3. Polycythemia vera
associated most often with JAK2 mutation in up to 80% of cases:a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome fibrosis, and increased myeloid and erythroid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
4. Essential Thrombocythemia
associated with JAK2 mutation in up to 20% of cases and MPL (thrombopoietin receptor) mutation in up to 15% of cases:a. Cellular phase - increased large megakaryocytes with fibrosis and little increase in other bone marrow elements
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
These disorders are still being revised according to more specific genetic mutations and how often patients end in a fibrotic marrow event.
In 2005, the discovery of the JAK2 V617F mutation provided some evidence to suggest a common pathogenesis for the Philadelphia Chromosome negative MPDs.