This leukemia is thought to derive from the transformation of a multipotent myeloid progenitor cell. In the adult patient multilineage dysplasia is a common finding and in some cases a minority of myeloid blast cells is present.
The blast cells show one or more megakaryocytic markers (i.e. Factor VIII, CD61, CD41, or CD42), they test negative when using the anti-myeloperoxidase monoclonal antibody and never show coordinated expression of lymphoid markers, though isolated CD2 or CD7 positivity can be found on some occasions. The CD34, CD13 and CD33 markers are positive in a substantial fraction of cases, as is the case with the CD36/thrombospondin receptor.
The myeloperoxidase stain is negative by light microscopy, but ultrastructural peroxidase activity with a specific peri-nuclear staining pattern can be detected at the electron microscopy level.

The disease is rare and, due to difficulty in diagnosis, its exact incidence is not known. Reasonably, it may account for approximately 1-2% of all de novo acute myeloid leukemias (AML) in the adult population, but the incidence in the pediatric age group is higher, partly due to an association with Down syndrome.

The presentation is usually acute, though AMegL may develop after myelodysplastic syndrome or chronic myelogenous leukemia (CML).
In some cases acute myelofibrosis is the presentation picture.
AMegL should be distinguished from AML with megakaryoblastic involvement showing a minority of megakaryoblasts.
In children there is an association with Down syndrome.

The blast cell morphology varies from case to case. In some patients the blasts are undifferentiated and the diagnosis requires immunophenotyping or electron microscopy studies. Dysmegakaryocytopoiesis is rather frequent. Other patients may show bleb-forming blasts, but this feature is nor specific for megakaryoblasts. Micromegakaryocytes can be frequently seen.

The bone biopsy almost invariably shows fibrosis, which can be extensive in up to 75% of the cases.
Spleen enlargement is frequently seen in children, less frequently in adults.

Myeloablative treatment followed, whenever possible, by allogeneic or autologous bone marrow transplant is the treatment of choice

In general, the prognosis is severe. 30-to-50 % of the adult patients achieve a complete morphologic remission, but the majority relapse within a few months. Median duration of CR and survival in a study was 10.6 months and 10.4 months, respectively. Some children may fare better, with a 50% 3-year event free survival in AML-M7 post Down Syndrome or with the t(1;22) (see below). Prognosis is dismal in children with other cytogenetic abnormalities.

a) Adults
There is no cytogenetic anomaly that is specific for AML-M7. The karyotype is abnormal in the vast majority of cases with complex aberrations (i.e. 3 or more clonal aberrations) occurring more frequently than in other AMLs. -5/5q- and/or -7/7q+ are found, as a rule, in virtually all cases with complex karyotype, which globally account for 70-80% of abnormal cases.
3q21 or q26 aberrations are found in 20-30% of the cases; the t(9;22) is another recurrent chromosome aberrations in de novo AML-M7.
Trisomy 19 and 21 may occur in de novo as well as in secondary AML-M7. They are the most frequently occurring chromosome gains and they may be associated with any of the cytogenetic group listed above.

b) Children
The t(1;22)(p13;q13) is specifically associated with children AML-M7, being found in approximately half of the cases. The remaining patients may show +21 (irrespective of the association with Down syndrome), +19, +8. The karyotype may be normal in approximately 10% of the cases.

Partial trisomy 19, involving the q13 band, can be shown to occur at a 20-30% incidence by comparative genomic hybridization
The t(1;22)(p13;q13) fuses the OTT(RBM15) gene on 1p13 to the MAL(MKL1) gene on chromosome 22, leading to the OTT-MAL fusion gene on the derivative 22

The fusion gene OTT-MAL is on the der(22) chromosome and contains almost all of the sequences of each gene.

Sometimes presenting as "acute myelofibrosis"