Saida Satoshi
Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Int J Hematol. 2016 Apr;103(4):365-72. doi: 10.1007/s12185-016-1959-5. Epub 2016 Feb 24.
Children with Down syndrome (DS) have a markedly increased risk of leukemia. They are at particular risk of acute megakaryoblastic leukemia, known as myeloid leukemia associated with DS (ML-DS), the development of which is closely linked to a preceding temporary form of neonatal leukemia called transient abnormal myelopoiesis (TAM). Findings from recent clinical and laboratory studies suggest that constitutional trisomy 21 and GATA1 mutation(s) cause TAM, and that additional genetic alteration(s) including those in epigenetic regulators and signaling molecules are involved in the progression from TAM to ML-DS. Thus, this disease progression represents an important model of multi-step leukemogenesis. The present review focuses on the evolutionary process of TAM to ML-DS, and advances in the understanding of perturbed hematopoiesis in DS with respect to GATA1 mutation and recent findings, including cooperating genetic events, are discussed.
患有唐氏综合征（DS）的儿童患白血病的风险显著增加。他们尤其易患急性巨核细胞白血病，即与唐氏综合征相关的髓系白血病（ML-DS），其发生与一种先前的新生儿白血病临时形式——短暂异常髓系造血（TAM）密切相关。近期临床和实验室研究结果表明，染色体21三体和GATA1突变导致TAM，并且包括表观遗传调节因子和信号分子在内的其他基因改变参与了从TAM到ML-DS的进展。因此，这种疾病进展代表了多步骤白血病发生的重要模型。本综述聚焦于TAM向ML-DS的演变过程，并讨论了在GATA1突变以及包括协同遗传事件在内的近期研究结果方面，对唐氏综合征中造血功能紊乱认识的进展。
