Acute megakaryoblastic leukemia (AMKL) is a form of leukemia where a majority of the blasts are megakaryoblastic.
It is classified under AML-M7 category of the French-American-British classification.
The latest WHO classification (2008, Lyon), classifies Acute Myeloid Leukemia into distinct subtypes, based on clinico-pathological and molecular features. Acute megakaryoblastic leukemia is placed under the AML-Not Otherwise Specified subcategory.
Diagnosis requires more than 20% Blasts in the marrow/ peripheral blood with more than 50% demonstrating megakaryocytic derivation by morphology, immunophenotypic or electron microscopic studies.
It is associated with GATA1, 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 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.
In the first three years of life, megakaryoblastic leukemia is the most common type of leukemia in patients with Down syndrome.
The morphology of cells was observed by means of bone marrow smear; the immunophenotype was detected by flow cytometry and immunohistochemistry assay.
Blasts more than 20%, with more than 50% of megakaryocytic phenotype.
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 (MPO) activity and stain negatively with Sudan black B. They are alpha naphthyl butyrate esterase negative and manifest variable alpha naphthyl 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 is by immunophenotyping or with electron microscopy (EM). Immunophenotyping using MoAb to megakaryocyte restricted antigen (CD41 and CD61) may be diagnostic.
Complete remission and long-term survival are more common in children than adults.
Prognosis depends upon the 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.