Target cell of leukemic transformation in acute megakaryoblastic leukemia

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Abstract
Acute megakaryoblastic leukemia (AMkL) is a newly defined acute leukemia in which the differentiation of proliferating blasts is arrested at the megakaryocytic precursor stage. In order to clarify whether a target cell of leukemic transformation in AMkL is a cell committed to megakaryocytic lineage, or a multipotential stem cell, we examined AMkL patients with regard to: a) the presence of myelodyplastic features in residual erythroid and granulocytic cells, b) coexistence of myeloperoxidase (MPO)-positive blasts with megakaryoblasts, and c) the presence of the same chromosomal abnormality in erythroid and granuloid colony-forming cells as seen in megakaryoblasts. Regarding the former two items, results were compared with those from megakaryoblastic crisis of chronic myelocytic leukemia (CML-MkBC) and transient myeloproliferative disorder in Down syndrome (DS-TMD), which are thought to be multipotential stem cell disorders. Among 18 patients with AMkL, three, all complicating myelofibrosis, had marked myelodysplastic changes of erythroid series and/or granulocytic series. In 4 out of 7 patients with CML-MkBC, 5 out of 8 patients with DS-TMD, and 7 out of 18 patients with AMkL, MPO-positive blasts, even though rare, were observed in addition to PPO-positive blasts. All except one of these patients with AMkL also showed complicating myelofibrosis. In one case of AMkL with myelofibrosis, chromosomal analysis of cultured cells of individual colonies revealed that all the analysable metaphases from both CFU-GM and BFU-E had the same chromosomal abnormality as megakaryoblasts. This study has clarified that a considerable proportion of AMkL cases, particularly those with complicating myelofibrosis or showing acute myelofibrosis, arise against the background of a multipotential stem cell disorder, even if blasts are exclusively megakaryocytic in phenotype.

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