SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities
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AuthorAndrades Delgado, Álvaro; Peinado Fernández, Paola; Álvarez Pérez, Juan Carlos; Sanjuan Hidalgo, Juan; García García, Daniel Jesús; Arenas Molina, Alberto Manuel; Matia González, Ana María; Medina Vico, Pedro Pablo
SWI/SNFBAF complexesChromatin remodelingEpigeneticsLymphomaLeukemiaMultiple myelomaSynthetic lethalityDrug resistance
Andrades, A... [et al.] SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities. Mol Cancer 22, 39 (2023). [https://doi.org/10.1186/s12943-023-01736-8]
SponsorshipAula de Investigacion sobre la Leucemia infantil: Heroes contra la Leucemia; Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2021-126111OB-I00; Junta de Andalucia PIGE-0440-2019 PI-0135-2020 P20_00688; University of Granada B-CTS-480-UGR20 OTRI-UGR P32_2020_001; Spanish Association Against Cancer LAB-AECC-2018 Spanish Government FPU17/00067; University of Granada; Programa Operativo de Empleo Juvenil y de la Iniciativa de Empleo Juvenil 2021-2023 8114; Scientific Foundation of the Spanish Association Against Cancer in Granada PRDGR21428SANJ; "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship; "UGR Plan Propio" contract - Spanish Ministry of Universities; European Union Next Generation FPU17/01258
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.