MSI2: Is This RNA-Binding Protein a Potential Therapeutic Target in Mantle Cell Lymphoma?

By: Joseph Fanelli
Posted: Tuesday, August 9, 2022

Musashi-2 (MSI2), an RNA-binding protein that maintains self-renewal and prevents differentiation in hematopoietic stem cells and embryonic stem cells, may play a key role in sustaining stemness, chemoresistance, and tumor cell survival in mantle cell lymphoma, according to findings presented at the European Hematology Association (EHA) 2022 Congress (Abstract P1295). The protein is a potential therapeutic target for this type of B-cell lymphoma, concluded Virginia Amador, PhD, of the University of Spain, Barcelona, and colleagues.

In this study, the authors integrated the differential gene-expression profile between SOX11-positive and SOX11-negative mantle cell lymphoma primary cases with stem cell–related genes, specific SOX11 ChIP-chip bound genes, and epigenomic data of mantle cell lymphoma.

The investigators found that SOX11-positive cases revealed enrichment in leukemic and hematopoietic stem cell gene signatures compared with SOX11-negative cases. MSI2 was identified as the most significant upregulated stem cell–related gene in SOX11-positive mantle cell lymphoma cases. SOX11 was directly bound to MSI2 regulatory regions, increasing the expression within in vitro mantle cell lymphoma cells.

MSI2 enhancers located in intronic regions were strongly activated in SOX11-positive cases, but not in SOX11-negative mantle cell lymphoma cell lines and primary cases, according to the investigators. The upregulation of MSI2 was significantly associated with chemoresistance and poor overall survival, independent of common risk factors in patients with mantle cell lymphoma, the authors said.

Disclosure: For full disclosures of the study authors, visit ehaweb.org.

EHA 2022 Congress

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