Functional Genomics and Department of Pediatric Hemato-Oncology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
J Clin Invest. 2012 Mar;122(3):807-10. doi: 10.1172/JCI62372. Epub 2012 Feb 22.
Children with Down syndrome (DS) have a markedly increased risk of developing acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia compared with that of children without DS. Despite recent breakthroughs, it is not clear which genes on chromosome 21, the chromosome that is trisomic in individuals with DS, cause this predisposition. In this issue of the JCI, Malinge et al. report their loss- and gain-of-function experiments in mouse and human cells that show that increased expression of the kinase encoded by the chromosome 21 gene DYRK1A suppresses the nuclear factor of activated T cells pathway and promotes AMKL. Interestingly, the same protein has been suggested to contribute to the reduced risk of epithelial cancers in adults with DS, leading to the possibility that it could be proleukemic in children and antitumorigenic in adults.
唐氏综合征（DS）患儿发生急性巨核细胞白血病（AMKL）和急性淋巴细胞白血病的风险显著高于非 DS 患儿。尽管最近取得了一些突破，但尚不清楚 21 号染色体上的哪些基因（DS 患者的染色体三体）导致了这种易感性。在本期 JCI 中，Malinge 等人报告了他们在小鼠和人类细胞中的功能丧失和获得实验，结果表明，21 号染色体基因 DYRK1A 编码的激酶表达增加会抑制激活 T 细胞核因子通路，并促进 AMKL。有趣的是，同一种蛋白已被认为有助于降低 DS 成年患者患上皮癌的风险，这提示该蛋白在儿童中可能具有促白血病作用，而在成人中则具有抗肿瘤作用。
