Institute of Experimental Cancer Research, CCC and University Hospital of Ulm, 89081 Ulm, Germany.
Department of Internal Medicine I, Center for Internal Medicine, University Medical Center Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Cell Rep. 2016 Jul 12;16(2):498-507. doi: 10.1016/j.celrep.2016.05.094. Epub 2016 Jun 23.
Homeobox genes are known to be key factors in leukemogenesis. Although the TALE family homeodomain factor Meis1 has been linked to malignancy, a role for MEIS2 is less clear. Here, we demonstrate that MEIS2 is expressed at high levels in patients with AML1-ETO-positive acute myeloid leukemia and that growth of AML1-ETO-positive leukemia depends on MEIS2 expression. In mice, MEIS2 collaborates with AML1-ETO to induce acute myeloid leukemia. MEIS2 binds strongly to the Runt domain of AML1-ETO, indicating a direct interaction between these transcription factors. High expression of MEIS2 impairs repressive DNA binding of AML1-ETO, inducing increased expression of genes such as the druggable proto-oncogene YES1. Collectively, these data describe a pivotal role for MEIS2 in AML1-ETO-induced leukemia.
同源盒基因是白血病发生的关键因素。虽然 TALE 家族同源域因子 Meis1 与恶性肿瘤有关，但 MEIS2 的作用尚不清楚。在这里，我们证明 MEIS2 在 AML1-ETO 阳性急性髓系白血病患者中高表达，并且 AML1-ETO 阳性白血病的生长依赖于 MEIS2 的表达。在小鼠中，MEIS2 与 AML1-ETO 合作诱导急性髓系白血病。MEIS2 与 AML1-ETO 的 Runt 结构域强烈结合，表明这些转录因子之间存在直接相互作用。MEIS2 的高表达会损害 AML1-ETO 的抑制性 DNA 结合，从而诱导可药物治疗的原癌基因 YES1 等基因的表达增加。总之，这些数据描述了 MEIS2 在 AML1-ETO 诱导的白血病中的关键作用。
