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Preprint WatchMildNovember 6th, 2026

BCL10 Gain-of-Function Impairs Germinal Center Participation by Naive B Cells and Cooperates with BCL6 to Drive Extrafollicular Diffuse Large B-Cell Lymphoma

Chahar, D.; Youssfi, A. A.; Coughlin, C. A.; Huang, H.-T.; Kuan, V. L. S.; Saralamma, V. V. G.; Lekakis, M.; Huynh, D.; Maura, F.; Amador, C.; Bilbao Cortes, D.

BCL10 gain-of-function mutations activate CARD11-BCL10-MALT1 signalling, drive resistance to multiple drug classes, and cooperate with BCL6 translocation to produce extrafollicular non-germinal-centre DLBCL.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

This preprint shows that BCL10 gain-of-function lesions, which activate CARD11-BCL10-MALT1 signalling and confer resistance across drug classes, block naive B-cell entry into germinal centres and cooperate with BCL6 translocation to generate extrafollicular diffuse large B-cell lymphoma. Claidex holds one MALT1 failure, ono-7018-malt1-nhl-cll-phase1-strategic-discontinuation, a Phase 1 programme in relapsed or refractory non-Hodgkin lymphoma and chronic lymphocytic leukaemia discontinued for strategic reasons rather than on efficacy. The preprint does not test a MALT1 inhibitor, so it neither supports nor contradicts that programme directly. It does sharpen the selection question, because if pathological CBM activation arises through BCL10 lesions that also confer broad drug-class resistance, a MALT1 inhibitor needs the BN2/C1 subgroup defined prospectively rather than a general lymphoma population. Severity is MILD on one prior non-efficacy failure.

Abstract excerpt

BCL10 gain-of-function mutations activate CARD11-BCL10-MALT1 signalling, drive resistance to multiple drug classes, and cooperate with BCL6 translocation to produce extrafollicular non-germinal-centre DLBCL.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.