MRC Weatherall Institute of Molecular Medicine, University of Oxford, United Kingdom of Great Britain and Northern Ireland.
IUBMB Life. 2020 Jan;72(1):119-130. doi: 10.1002/iub.2197. Epub 2019 Nov 26.
Myeloid leukaemia of Down syndrome (ML-DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It has a unique clinical course, being preceded by a pre-leukaemic condition known as transient abnormal myelopoiesis (TAM), and provides an excellent model to study multistep leukaemogenesis. Both TAM and ML-DS blasts carry acquired N-terminal truncating mutations in the erythro-megakaryocytic transcription factor GATA1. These result in exclusive production of a shorter isoform (GATA1s). The majority of TAM cases resolve spontaneously without the need for treatment; however, around 10% acquire additional cooperating mutations and transform to leukaemia, with differentiation block and clinically significant cytopenias. Transformation is driven by the acquisition of additional mutation(s), which cooperate with GATA1s to perturb normal haematopoiesis.
唐氏综合征相关髓系白血病（ML-DS）是一种独特的急性巨核细胞/红系白血病，仅见于唐氏综合征患儿（21 号染色体三体性）。它具有独特的临床病程，此前存在一过性髓系增生异常（TAM）这一前白血病状态，为研究多步骤白血病发生提供了极好的模型。TAM 和 ML-DS 白血病细胞均携带红细胞巨核细胞转录因子 GATA1 的 N 端截断获得性突变。这些突变导致仅产生较短的同工型（GATA1s）。大多数 TAM 病例可自发消退而无需治疗；然而，约 10%的病例会获得额外的协同突变并转化为白血病，伴有分化阻滞和临床上显著的细胞减少。转化是由获得额外的突变驱动的，这些突变与 GATA1s 协同作用，扰乱正常造血。
