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

Molecular Cancer

Review

Juan Sanjuan-Hidalgo¹  Alberto M. Arenas²  Ana M. Matia-González²  Alvaro Andrades²  Juan Carlos Alvarez-Perez²  Pedro P. Medina²  Paola Peinado³  Daniel J. García⁴ 

[1] Department of Biochemistry and Molecular Biology I. Faculty of Sciences, University of Granada, Granada, Spain;GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain;Department of Biochemistry and Molecular Biology I. Faculty of Sciences, University of Granada, Granada, Spain;GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain;Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain;Department of Biochemistry and Molecular Biology I. Faculty of Sciences, University of Granada, Granada, Spain;GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain;Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain;The Francis Crick Institute, London, UK;GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain;Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Granada, Spain;

关键词: SWI/SNF;    BAF complexes;    Chromatin remodeling;    Epigenetics;    Lymphoma;    Leukemia;    Multiple myeloma;    Synthetic lethality;    Drug resistance;   

DOI  :  10.1186/s12943-023-01736-8

 received in 2022-12-01, accepted in 2023-01-30,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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