No specific chromosome abnormalities are described for these AMLs. Complex karyotypes with multiple structural abnormalities are common. Chromosomes 5 and 7 appear to be affected frequently.[57,67,68] One study indicates that abnormalities of chromosomes 5 and/or 7 correlate with significantly shorter survival times.
Acute megakaryoblastic leukemia (FAB Classification M7)
Acute megakaryoblastic leukemia, in which 50% or more of blasts are of the megakaryocyte lineage, occurs in all age groups and comprises approximately 3% to 5% of cases of AML. Clinical features include cytopenias; dysplastic changes in neutrophils and platelets; rare organomegaly, except in children with t(1; 22); lytic bone lesions in children; and association with mediastinal germ cell tumors in young adult males.[57,70,71]
Morphologic and cytochemical features include the following:[57,70,72]
- Medium- to large-sized megakaryoblasts with round or indented nucleus and one or more nucleoli.
- Agranular, basophilic cytoplasm with pseudopod formation.
- Lymphoblast-like morphology (high nuclear-cytoplasmic ratio) in some cases.
- Circulating micromegakaryocytes, megakaryoblastic fragments, dysplastic large platelets, and hypogranular neutrophils.
- Stromal pattern of marrow infiltration mimicking a metastatic tumor in infants.
- Negative stains for SBB and MPO.
- Blasts reactive with PAS, acid phosphatase, and nonspecific esterase.
Immunophenotyping reveals megakaryoblast expression of one or more platelet glycoproteins: CD41 (glycoprotein IIb/IIIa) and/or CD61 (glycoprotein IIIa). Myeloid markers CD13 and CD33 may be positive; CD36 is typically positive. Blasts are negative with the anti-MPO antibody and other markers of myeloid differentiation. In bone marrow biopsies, megakaryocytes and megakaryoblasts may react positively to antibodies for Factor VIII. The differential diagnosis includes minimally differentiated AML, acute panmyelosis with myelofibrosis, ALL, pure erythroid leukemia, and blastic transformation of chronic myeloid leukemia or idiopathic myelofibrosis and metastatic tumors in the bone marrow (particularly in children). (Refer to the PDQ summary on Chronic Myeloproliferative Neoplasms Treatment for more information on chronic myeloid leukemia or idiopathic myelofibrosis).
No unique chromosomal abnormalities are associated with acute megakaryoblastic leukemia in adults.[57,73] In children, particularly infants, a distinct clinical presentation may be associated with t(1:22)(p13; q13).[70,72] The prognosis for this type of acute leukemia is poor.[74,75]