Transcriptional regulation of megakaryopoiesis: thrombopoietin signaling and nuclear factors.

Purpose Of Review: Thrombopoietin, the primary regulator of megakaryopoiesis, acts by modulating several nuclear transcription factors. This review focuses on recent studies that have provided new insights into the functional roles of these proteins.

Recent Findings: Among the transcription factors responsible for megakaryopoiesis, important roles for the signal transducer and activator of transcription and Forkhead box proteins have been defined. In addition, in the past several years, two new groups of transcription factors have been found to be affected by thrombopoietin signaling, homeodomain-containing HOX proteins and hypoxia-inducible factor. The HOX transcription factors, which play key roles in body pattern development, are also expressed in adult hematopoietic stem cells and play pivotal roles in their proliferation. Thrombopoietin controls the levels of expression and modifies the function of homeodomain proteins in thrombopoietin-responsive leukemic cells and in primary immature hematopoietic cells. Levels of hypoxia-inducible factor, a master transcription factor required for the adaptation to hypoxic conditions, is also affected by thrombopoietin in these cells.

Summary: The discovery that a diverse range of transcription factors are downstream effectors of thrombopoietin helps to explain the molecular mechanisms by which the hormone affects hematopoiesis.