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

• Published in: Molecular cancer 2023-02, Vol.22 (1), p.39-39, Article 39
• Main Authors: Andrades, Alvaro, Peinado, Paola, Alvarez-Perez, Juan Carlos, Sanjuan-Hidalgo, Juan, García, Daniel J, Arenas, Alberto M, Matia-González, Ana M, Medina, Pedro P
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents; Antineoplastic drugs; B cells; BAF complexes; Bone marrow; Cancer; Cell differentiation; Chromatin; Chromatin remodeling; DNA repair; Drug resistance; Epigenetic inheritance; Epigenetics; Gene expression; Genes, Tumor Suppressor; Health aspects; Hematologic Neoplasms - genetics; Hematology; Hematopoietic stem cells; Humans; Lethality; Leukemia; Lymphoma; Lymphomas; Malignancy; Mutation; Neoplasms - metabolism; Proteins; Review; Roles; Sucrose; SWI/SNF; SWI/SNF complex; Transcription factors; Tumor suppressor genes; Tumors
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-023-01736-8

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.