Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Leukemia. 2021 Dec;35(12):3352-3360. doi: 10.1038/s41375-021-01414-y. Epub 2021 Sep 13.
Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal myelopoiesis (TAM), which is self-limited expansion of fetal liver-derived megakaryocyte progenitors. An array of international studies has led to consensus in treating ML-DS with reduced-intensity chemotherapy, leading to excellent outcomes. In addition, studies performed in the past 20 years have revealed many of the genetic and epigenetic features of the tumors, including GATA1 mutations that are arguably associated with all cases of both TAM and ML-DS. Despite these advances in understanding the clinical and biological aspects of ML-DS, little is known about the mechanisms of relapse. Upon relapse, patients face a poor outcome, and there is no consensus on treatment. Future studies need to be focused on this challenging aspect of leukemia in children with DS.
唐氏综合征患儿罹患白血病的风险升高，尤其是骨髓性白血病（ML-DS）。这种恶性肿瘤常以前期短暂性髓系增生异常（TAM）为前驱，其为胎儿肝脏来源的巨核细胞前体细胞的自限性扩增。一系列国际研究达成共识，采用低强度化疗治疗 ML-DS，从而取得了极好的效果。此外，过去 20 年来开展的研究揭示了肿瘤的许多遗传和表观遗传特征，包括 GATA1 突变，该突变可认为与 TAM 和 ML-DS 的所有病例均相关。尽管在了解 ML-DS 的临床和生物学方面取得了这些进展，但对于复发的机制仍知之甚少。复发后，患者预后不良，且对治疗尚无共识。未来的研究需要集中在 DS 患儿白血病这一极具挑战性的方面。
