SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities Andrades 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/SNF BAF complexes Chromatin remodeling Epigenetics Lymphoma Leukemia Multiple myeloma Synthetic lethality Drug resistance 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. 2023-03-29T07:58:08Z 2023-03-29T07:58:08Z 2023-02-21 info:eu-repo/semantics/article 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] https://hdl.handle.net/10481/80921 10.1186/s12943-023-01736-8 eng http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional BMC