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Targeting the DNA damage response through TBL1X in mantle cell lymphoma.


ABSTRACT:

Abstract

Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma characterized by significant genomic instability. Patients with MCL who progress on targeted therapies have a short survival; thus, novel therapeutic strategies are urgently needed. Overexpression of transducin β-like protein 1 X-linked (TBL1X) has been documented in several types of cancer and associated with poor prognosis. TBL1X is a critical regulator of multiple oncogenic networks; however, its function in MCL has not been explored. Our data show that, unlike normal B cells, MCL cells express abundant levels of TBL1X and that genetic knockdown of TBL1X and treatment with tegavivint (Iterion), a first-in-class small molecule targeting TBL1X, promote MCL cell death in vitro and in vivo. Moreover, TBL1X controls

SUBMITTER: Pray B 

PROVIDER: S-EPMC12034073 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature

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