SWI/SNF complexes in hematological malignancies - biological implications and therapeutic opportunities - Review

Sep 24, 2026

Hematological malignancies are a highly heterogeneous set of diseases distinguished by diverse molecular and phenotypic features. SWI/SNF chromatin remodeling complexes regulate gene expression and are crucial for maintenance and differentiation in hematopoietic stem cells. Recurrent alterations in SWI/SNF subunits, particularly ARID1A/1B/2, SMARCA2/4, and BCL7A, occur across many lymphoid and myeloid malignancies, often suggesting tumor-suppressor loss of function. Yet some contexts involve tumor maintenance or oncogenic functions.

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Abstract

Background

Andrades et al. Molecular Cancer (2023) 22:39 [https://doi.org/10.1186/s12943-023-01736-8](https://doi.org/10.1186/s12943-023-01736-8) Molecular Cancer REVIEW Open Access SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities Alvaro Andrades1,2,3†, Paola Peinado 1,2,3,4†, Juan Carlos Alvarez‑Perez1,2,3†, Juan Sanjuan‑Hidalgo1,2, Daniel J. García2,5, Alberto M. Arenas 1,2,3, Ana M. Matia‑González 1,2,3 and Pedro P. Medina 1,2,3* Abstract Hematological malignancies are a highly heterogeneous group of diseases with varied molecular and phenotypi‑ cal 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 differentia‑ tion 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. Therecurrent alterations of SWI/SNF subunits highlight not only the biological relevance of SWI/SNF complexes in hema‑ tological 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 com‑ plexes 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. Keywords SWI/SNF, BAF complexes, Chromatin remodeling, Epigenetics, Lymphoma, Leukemia, Multiple myeloma, Synthetic lethality, Drug resistance †Alvaro Andrades, Paola Peinado and Juan Carlos Alvarez‑Perez shared first authorship. *Correspondence: Pedro P. Medina [pedromedina@ugr.es](pedromedina@ugr.es) 1 Department of Biochemistry and Molecular Biology I. Faculty of Sciences, University of Granada, Granada, Spain 2 GENYO, Centre for Genomics and Oncological Research: Pfizer/ University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain 3 Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), Granada, Spain 4 Present Address: The Francis Crick Institute, London, UK 5 Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Granada, Spain © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The

FAQs

What roles do SWI/SNF chromatin remodeling complexes play in hematopoietic cells?

SWI/SNF complexes regulate gene expression and are essential for processes such as maintenance and differentiation in hematopoietic stem cells.

Which SWI/SNF subunits are frequently altered in hematological malignancies?

Alterations are especially recurrent in ARID1A/1B/2, SMARCA2/4, and BCL7A across a wide range of lymphoid and myeloid malignancies.

How can SWI/SNF mutations be therapeutically relevant?

Mutations can confer resistance to several antineoplastic agents and can create synthetic lethality relationships with other SWI/SNF or non-SWI/SNF proteins that may be targeted.

Sep 24, 2026

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