biostudies-literatureUnknown9(8)Pray B<h4>Abstract</h4>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 Blood advances2006-2018https://www.ebi.ac.uk/biostudies/studies/S-EPMC12034073biostudies-literatureTargeting the DNA damage response through TBL1X in mantle cell lymphoma.PMC12034073Sehgal LChan WKHinterschied CYalowich JPray BJain NBaiocchi RABaiocchi EKoirala SCarvajal-Moreno JHanel WLeon SNishat STsyba LAlinari LJindal USingh SBarta BHout IfalseTargeting the DNA damage response through TBL1X in mantle cell lymphoma.<h4>Abstract</h4>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 2025-01-01T00:00:00Z2025 Apr2026-06-02T20:39:51.851Z2025-06-27T03:05:26.261ZS-EPMC120340734000975310.1182/bloodadvances.2024015769