Hall Trent, Gurbuxani Sandeep, Crispino John D
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.
Section of Hematopathology, Department of Pathology, University of Chicago, Chicago, IL.
Blood. 2024 May 30;143(22):2245-2255. doi: 10.1182/blood.2023020817.
The spectrum of myeloid disorders ranges from aplastic bone marrow failure characterized by an empty bone marrow completely lacking in hematopoiesis to acute myeloid leukemia in which the marrow space is replaced by undifferentiated leukemic blasts. Recent advances in the capacity to sequence bulk tumor population as well as at a single-cell level has provided significant insight into the stepwise process of transformation to acute myeloid leukemia. Using models of progression in the context of germ line predisposition (trisomy 21, GATA2 deficiency, and SAMD9/9L syndrome), premalignant states (clonal hematopoiesis and clonal cytopenia of unknown significance), and myelodysplastic syndrome, we review the mechanisms of progression focusing on the hierarchy of clonal mutation and potential roles of transcription factor alterations, splicing factor mutations, and the bone marrow environment in progression to acute myeloid leukemia. Despite major advances in our understanding, preventing the progression of these disorders or treating them at the acute leukemia phase remains a major area of unmet medical need.
髓系疾病的范围从以完全缺乏造血功能的空骨髓为特征的再生障碍性骨髓衰竭到骨髓空间被未分化的白血病母细胞取代的急性髓系白血病。对大量肿瘤群体以及单细胞水平进行测序的能力的最新进展，为向急性髓系白血病转化的逐步过程提供了重要见解。利用在种系易感性（21三体、GATA2缺乏和SAMD9/9L综合征）、癌前状态（克隆性造血和意义未明的克隆性血细胞减少）以及骨髓增生异常综合征背景下的进展模型，我们回顾了进展机制，重点关注克隆突变的层级以及转录因子改变、剪接因子突变和骨髓环境在进展为急性髓系白血病中的潜在作用。尽管我们在认识上取得了重大进展，但预防这些疾病的进展或在急性白血病阶段对其进行治疗仍然是一个尚未满足的主要医疗需求领域。
