Analysis of leukemogenesis caused by disordered transcription regulation

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GATA1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. Acquired mutations deleting the N-terminal region of GATA1 protein are frequently found in acute megakaryoblastic leukemia (AMKL) and transient myeloproliferative disorder (TMD) in children with Down syndrome. We found that full length of GATA1 could restrict proliferation of megakaryocyte progenitors derived from livers of GATA1-null fetus and cell line originally established from AMKL patients, whereas mutant GATA1s lacking consensus motif essential for the interaction sites with Rb protein could not support the GATA1 function on the growth regulation of immature megakaryocytes. This finding indicates that the GATA1 function supported by interaction with Rb protein is involved in the onset of TMD.