Bouligny Ian M, Maher Keri R, Grant Steven
Division of Hematology and Oncology, Department of Internal Medicine, Virginia Commonwealth University Massey Cancer Center, Richmond, VA 23298, USA.
Cancers (Basel). 2023 Jun 22;15(13):3292. doi: 10.3390/cancers15133292.
The characterization of the molecular landscape and the advent of targeted therapies have defined a new era in the prognostication and treatment of acute myeloid leukemia. Recent revisions in the European LeukemiaNet 2022 guidelines have refined the molecular, cytogenetic, and treatment-related boundaries between myelodysplastic neoplasms (MDS) and AML. This review details the molecular mechanisms and cellular pathways of myeloid maturation aberrancies contributing to dysplasia and leukemogenesis, focusing on recent molecular categories introduced in ELN 2022. We provide insights into novel and rational therapeutic combination strategies that exploit mechanisms of leukemogenesis, highlighting the underpinnings of splicing factors, the cohesin complex, and chromatin remodeling. Areas of interest for future research are summarized, and we emphasize approaches designed to advance existing treatment strategies.
分子格局的特征描述以及靶向治疗的出现，为急性髓系白血病的预后和治疗开创了一个新时代。欧洲白血病网络（European LeukemiaNet）2022年指南的最新修订，进一步明确了骨髓增生异常肿瘤（MDS）和急性髓系白血病（AML）之间在分子、细胞遗传学及治疗相关方面的界限。本综述详细阐述了导致发育异常和白血病发生的髓系成熟异常的分子机制和细胞途径，重点关注欧洲白血病网络2022年引入的最新分子类别。我们深入探讨了利用白血病发生机制的新型合理治疗联合策略，突出了剪接因子、黏连蛋白复合体和染色质重塑的基础。总结了未来研究的关注领域，并强调旨在推进现有治疗策略的方法。
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