Analysis of leukemogenesis caused by disordered transcription regulation

GATA 1是红系/巨核细胞分化所必需的转录因子。缺失GATA 1蛋白N-末端区域的获得性突变经常在患有唐氏综合征的儿童的急性巨核细胞白血病（AMKL）和短暂性骨髓增生性疾病（TMD）中发现。我们发现，全长GATA 1可以限制来自GATA 1-null胎儿肝脏的巨核祖细胞和最初从AMKL患者建立的细胞系的增殖，而缺乏与Rb蛋白相互作用位点必需的共有基序的突变GATA 1不能支持GATA 1对未成熟巨核细胞的生长调节功能。这一发现表明，GATA 1的功能支持的相互作用与Rb蛋白参与了TMD的发病。

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.