血液恶性肿瘤是一组高度异质性的疾病，具有各种分子和表型特征。SWI/SNF (SWItch/Sucrose Non-Fermentable) 染色质重塑复合物在基因表达调控中扮演重要角色，对于造血干细胞的维持和分化等过程至关重要。此外，SWI/SNF复合物亚单位的改变，特别是在ARID1A/1B/2、SMARCA2/4和BCL7A中，在各种淋巴和髓系恶性肿瘤中高度复发。大多数遗传改变导致亚单位功能丧失，提示其具有肿瘤抑制作用。然而，在某些疾病背景下，SWI/SNF亚单位也可能需要用于肿瘤维持甚至起到肿瘤发生作用。SWI/SNF亚单位的复发性改变不仅突显了SWI/SNF复合物在血液恶性肿瘤中的生物学相关性，还突显了其临床潜力。特别是，越来越多的证据表明，SWI/SNF复合物亚单位的突变会使多种常用于治疗血液恶性肿瘤的抗肿瘤药物失去疗效。此外，SWI/SNF亚单位的突变经常与其他SWI/SNF或非SWI/SNF蛋白产生合成致死关系，这些关系在治疗上可以被利用。总之，SWI/SNF复合物在血液恶性肿瘤中经常被改变，某些SWI/SNF亚单位可能是肿瘤维持的必需品。这些改变以及它们与SWI/SNF和非SWI/SNF蛋白的合成致死关系，可以在治疗多种血液肿瘤时得到药物利用。 © 2023. 作者(们)。

Hematological malignancies are a highly heterogeneous group of diseases with varied molecular and phenotypical characteristics. SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes play significant roles in the regulation of gene expression, being essential for processes such as cell maintenance and differentiation in hematopoietic stem cells. Furthermore, alterations in SWI/SNF complex subunits, especially in ARID1A/1B/2, SMARCA2/4, and BCL7A, are highly recurrent across a wide variety of lymphoid and myeloid malignancies. Most genetic alterations cause a loss of function of the subunit, suggesting a tumor suppressor role. However, SWI/SNF subunits can also be required for tumor maintenance or even play an oncogenic role in certain disease contexts. The recurrent alterations of SWI/SNF subunits highlight not only the biological relevance of SWI/SNF complexes in hematological malignancies but also their clinical potential. In particular, increasing evidence has shown that mutations in SWI/SNF complex subunits confer resistance to several antineoplastic agents routinely used for the treatment of hematological malignancies. Furthermore, mutations in SWI/SNF subunits often create synthetic lethality relationships with other SWI/SNF or non-SWI/SNF proteins that could be exploited therapeutically. In conclusion, SWI/SNF complexes are recurrently altered in hematological malignancies and some SWI/SNF subunits may be essential for tumor maintenance. These alterations, as well as their synthetic lethal relationships with SWI/SNF and non-SWI/SNF proteins, may be pharmacologically exploited for the treatment of diverse hematological cancers.© 2023. The Author(s).