Induction of megakaryocytic differentiation in primary human erythroblasts- A physiological basis for leukemic lineage plasticity

In myelodysplasias and acute myeloid leukemias, abnormalities in erythroid development often parallel abnormalities in megakaryocytic development. Ery throleukemic cells in particular have been shown to possess the potential t o undergo megakaryocytic differentiation in response to a variety of stimul i. Whether or not such lineage plasticity occurs as a consequence of the le ukemic phenotype has not previously been addressed. In this study, highly p urified primary human erythroid progenitors were subjected to stimuli known to induce megakaryocytic differentiation in erythroleukemic cells. Remarka bly, the primary erythroid progenitors rapidly responded with morphological and immunophenotypic evidence of megakaryocytic differentiation, equivalen t to that seen in erythroleukemic cells. Even erythroblasts expressing high levels of hemoglobin manifested partial megakaryocytic differentiation. Th ese results indicate that the lineage plasticity observed in erythroleukemi c cells reflects an intrinsic property of cells in the erythroid lineage ra ther than an epiphenomenon of leukemic transformation.