B-Cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development and Proinflammatory Signatures in Myeloma Model

Authors

Tabish Hussain
Matthew D Bramble
Bin Liu
Martin C Abba
Marta Chesi
C Marcelo Aldaz

Language

English

Publication Date

11-1-2025

Journal

Blood Neoplasia

DOI

10.1016/j.bneo.2025.100153

PMID

41090157

PMCID

PMC12517091

PubMedCentral® Posted Date

8-4-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk^∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk^∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic plasmacytomas and lymphomas. Transcriptome profiling from bone marrow derived CD138+ plasma cells and plasmablastic tumors revealed enrichment of biofunctions related to tumorigenic phenotype and inflammation activation upon Wwox deletion in Vk^∗MYC mice. Wwox KO plasmablastic tumors displayed mutations affecting classical cancer genes, DNA damage response (DDR) genes, as well as overexpression of Aid/Apobec family members associated to hypermutation and DDR mutational signatures. These findings illustrate the significant pathobiological effects of B-cell–specific Wwox deletion and support a relevant role for WWOX loss of function in B-cell neoplastic progression toward more aggressive phenotypes.

Published Open-Access

yes

Recommended Citation

Hussain, Tabish; Bramble, Matthew D; Liu, Bin; et al., "B-Cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development and Proinflammatory Signatures in Myeloma Model" (2025). Faculty, Staff and Student Publications. 5259.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5259