Acute megakaryoblastic leukemia

AML-M7 arises from malignant proliferation of megakaryoblasts, the precursor cells to platelets. In children with Down syndrome, it is preceded by transient abnormal myelopoiesis (TAM) in the neonatal period and is associated with GATA1 gene mutations, which impair normal megakaryocyte-erythroid differentiation. This Down syndrome-associated form generally has a favorable prognosis compared to non-Down syndrome cases. In adults and non-Down syndrome children, AML-M7 is often associated with t(1;22)(p13;q13) translocation (RBM15-MKL1 fusion) and tends to have a poor prognosis with resistance to standard chemotherapy. Clinically, patients present with cytopenias (anemia, thrombocytopenia despite megakaryocytic lineage, neutropenia), hepatosplenomegaly, and sometimes bone marrow fibrosis due to platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) release from megakaryoblasts, leading to a dry tap on bone marrow aspiration. Diagnosis requires immunophenotyping showing expression of megakaryocytic markers (CD41, CD42b, CD61) via flow cytometry, as megakaryoblasts often cannot be distinguished morphologically from other blasts and may not stain positive with myeloperoxidase. Electron microscopy can show platelet peroxidase activity. Treatment involves AML-type chemotherapy regimens, though non-Down syndrome cases often require more aggressive therapy including hematopoietic stem cell transplantation due to poor response rates.