Acute megakaryoblastic leukemia
Encyclopedia
Acute megakaryoblastic leukemia (AMKL) is a form of leukemia
where a majority of the blasts are megakaryoblastic.
It is classified under M7 in the French-American-British classification
.
This category of AML is associate with 30% or more blasts in the marrow, blast are identified as being of megakaryocyte lineage by; Expression of megakaryocyte specific antigens and platelet peroxidase reaction on electron microscopy.
, and risks are increased in individuals with Down syndrome
.
However, not all cases are associated with Down syndrome, and other genes can also be associated with AMKL.
Another related gene is MKL1
, which is also known as "MAL". This gene is a cofactor of serum response factor
.
In children; the same clinical presentation but with variable course especially in very young children; both leukocytosis and organomegaly may be present in children with M7. Complete remission and long term survival are more common in children than adults.
In the first three years of life megakaryoblastic leukemia is the most common type of leukemia in patients with Downs syndrome.
and immunohistochemistry
assay.
In blood and bone marrow smears megakaryoblasts are usually medium sized to large cells with a high nuclear-cytoplasmic ratio
. Nuclear chromatin
is dense and homogeneous. There is scanty, variable basophilic cytoplasm which may be vacuolated. An irregular cytoplasmic border is often noted in some of the megakaryoblasts and occasionally projections resembling budding atypical platelets are present. Megakaryoblasts lack myeloperoxidase
activity and stain negatively with Sudan black B. They are alpha naphthyl butyrate esterase negative and manifest variable alpha naphythyl acetate esterase activity usually in scattered clumps or granules in the cytoplasm. PAS staining also varies from negative to focal or granular positivity, to strongly positive staining. A marrow aspirate is difficult to obtain in many cases because of variable degree of myelofibrosis
. More precise identification by immunophenotyping or with electron microscopy (EM). Immunophenotyping using MoAb to megakaryocyte restricted antigen (CD41 and CD61
) may be diagnostic.
Another third of cases is found in Down syndrome. These cases have a reasonably fair prognosis.
The last third of cases may be heterogeneous, and carry a poor prognosis.
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...
where a majority of the blasts are megakaryoblastic.
It is classified under M7 in the 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...
.
This category of AML is associate with 30% or more blasts in the marrow, blast are identified as being of megakaryocyte lineage by; Expression of megakaryocyte specific antigens and platelet peroxidase reaction on electron microscopy.
Causes
It is associated with GATA1GATA1
Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1 gene....
, and risks are increased in individuals 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...
.
However, not all cases are associated with Down syndrome, and other genes can also be associated with AMKL.
Another related gene is MKL1
MKL1
MKL/megakaryoblastic leukemia 1 is a protein that in humans is encoded by the MKL1 gene.-Further reading:...
, which is also known as "MAL". This gene is a cofactor of serum response factor
Serum response factor
Serum response factor , also known as SRF, is a transcription factor.It is a member of the MADS box superfamily of transcription factors. This protein binds to the serum response element in the promoter region of target genes...
.
Signs and Symptoms
In adults include pancytopenia with low blast counts in the blood, myelofibrosis, an absence of lymphadenopathy and hepatosplenomegaly, poor response to chemotherapy,and short clinical course.In children; the same clinical presentation but with variable course especially in very young children; both leukocytosis and organomegaly may be present in children with M7. Complete remission and long term survival are more common in children than adults.
In the first three years of life megakaryoblastic leukemia is the most common type of leukemia in patients with Downs syndrome.
Diagnosis
The morphology of cells was observed by means of bone marrow smear; the immunophenotype was detected by flow cytometryFlow 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...
and immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
assay.
In blood and bone marrow smears megakaryoblasts are usually medium sized to large cells with a high nuclear-cytoplasmic ratio
NC ratio
The nuclear-cytoplasmic ratio is a measurement used in cell biology...
. Nuclear chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
is dense and homogeneous. There is scanty, variable basophilic cytoplasm which may be vacuolated. An irregular cytoplasmic border is often noted in some of the megakaryoblasts and occasionally projections resembling budding atypical platelets are present. Megakaryoblasts lack myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
activity and stain negatively with Sudan black B. They are alpha naphthyl butyrate esterase negative and manifest variable alpha naphythyl acetate esterase activity usually in scattered clumps or granules in the cytoplasm. PAS staining also varies from negative to focal or granular positivity, to strongly positive staining. A marrow aspirate is difficult to obtain in many cases because of variable degree of myelofibrosis
Myelofibrosis
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
. More precise identification by immunophenotyping or with electron microscopy (EM). Immunophenotyping using MoAb to megakaryocyte restricted antigen (CD41 and CD61
CD61
Integrin beta-3 or CD61 is a protein that in humans is encoded by the ITGB3 gene. CD61 is a cluster of differentiation found on thrombocytes.-Structure and function:...
) may be diagnostic.
Prognosis
Prognosis depends on cause. One third of cases is associated with a t(1;22)(p13;q13) mutation in children. These cases carry a poor prognosis.Another third of cases is found in Down syndrome. These cases have a reasonably fair prognosis.
The last third of cases may be heterogeneous, and carry a poor prognosis.
External links
- Histology at University of VirginiaUniversity of VirginiaThe University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
- Images at Nagoya UniversityNagoya UniversityNagoya University is one of the most prestigious universities in Japan. It can be seen in the several rankings such as shown below.-General Rankings:...