MCL Literature Feed

CD20-targeted CAR-T therapy induced durable remissions (>7 years) in MCL by triggering a lasting endogenous anti-tumor immune response (epitope spreading) despite a lack of CAR-T persistence.

A computational virtual screen of over 2.4 million compounds identified novel covalent BTK inhibitors, providing a foundation for developing next-generation therapeutics for MCL.

The dual HCK/BTK inhibitor KIN-8194 preclinically overcomes primary and acquired BTKi resistance in MCL by targeting HCK-mediated growth and adhesion, offering a novel therapeutic strategy.

The CDK9 inhibitor enitociclib overcomes resistance to both BTK inhibitors and CAR-T therapy, offering a potential new strategy for double-refractory mantle cell lymphoma.

The SOX11/PRDX2 axis is identified as a key regulator of chemoresistance in aggressive MCL by controlling redox homeostasis, offering a potential new therapeutic target.

PRMT5 promotes MCL growth via MYC-driven lipid metabolism reprogramming, identifying it as a poor prognostic marker and a novel therapeutic target with preclinical inhibitor activity.

The non-covalent BTK inhibitor pirtobrutinib demonstrates efficacy in mantle cell lymphoma patients who have progressed on prior covalent BTKi therapy, overcoming a common resistance mechanism.

This case report describes the rare phenomenon of biclonal mantle cell lymphoma, highlighting clonal heterogeneity and evolution which can impact diagnosis, disease progression, and therapeutic resistance.

This preclinical study identifies PLK-1 gene methylation as a key driver of bendamustine resistance, which was reversible with demethylating agents, suggesting a potential new therapeutic strategy.

Transformed MCL with triple-hit genetics (MYC/BCL2/BCL6 rearrangements) can be resistant to BTK inhibitors, identifying a novel genomic mechanism of treatment failure in this aggressive setting.

This review details the evolution of BTK inhibitors, highlighting improved toxicity with newer agents and the emergence of non-covalent BTKis and novel resistance mutations, impacting MCL treatment sequencing.

This preclinical study identifies SOX11 as an endogenous inhibitor of SAMHD1, which sensitizes mantle cell lymphoma to cytarabine, suggesting SOX11 status as a predictive biomarker for chemotherapy efficacy.

This B-ALL study reveals MALT1 inhibitors downregulate MYC, providing a novel mechanism and strong rationale for testing this strategy in aggressive, MYC-driven mantle cell lymphoma.

An editor's note highlights a preclinical study where a combined epigenetic therapy shows superior efficacy against MCL cells, suggesting a novel therapeutic strategy for clinical development.

An indirect comparison suggests brexucabtagene autoleucel provides superior response rates and progression-free survival over pirtobrutinib for MCL patients who have failed a prior covalent BTKi.

The PI3Ki zandelisib plus BTKi zanubrutinib combination shows high efficacy (74% ORR, 47% CR) with manageable toxicity in relapsed/refractory MCL, offering a promising chemotherapy-free regimen.

This preclinical study identifies DNMT3A-mediated metabolic reprogramming to oxidative phosphorylation as a novel ibrutinib resistance mechanism, which can be overcome by low-dose decitabine.

This preclinical study identifies that SOX11 upregulates the antioxidant PRDX2, promoting chemoresistance in aggressive MCL, and suggests PRDX2 as a novel therapeutic target to overcome drug resistance.

The CRM1 inhibitor KPT-330 induces protective autophagy in MCL cells; co-treatment with an autophagy inhibitor like chloroquine results in synergistic cell killing, suggesting a novel combination strategy.

Using computational screening and machine learning, this study identifies novel PIM2 inhibitors, presenting a potential new therapeutic target for future drug development in hematologic malignancies, including MCL.

This review, while focused on CLL, details the metabolic and toxicity profiles of covalent and non-covalent BTKis, informing MCL management strategies for adverse events and emerging resistance.

Palbociclib plus venetoclax shows preclinical synergy in ibrutinib-refractory MCL by downregulating MCL1, offering a chemo-free option for patients without RB1 deletion.

Phospho-flow cytometry reveals that high constitutive AKT and inducible STAT5/SYK B-cell receptor signaling activity predicts shorter survival and ibrutinib resistance, offering a functional biomarker for high-risk MCL.

This review details BTK inhibitor resistance mechanisms, particularly C481S mutations, and highlights non-covalent BTKi (pirtobrutinib) and PROTACs as key strategies to overcome relapse in MCL.

Targeting the epigenetic modifier KDM5 shows preclinical activity in mantle cell lymphoma, identifying a novel therapeutic vulnerability for potential future treatments.

Single-cell analysis reveals the HSP90-MYC-CDK9 network drives sequential BTKi and CAR-T resistance, suggesting co-targeting HSP90 and CDK9 as a novel strategy for dual-refractory MCL.

This workshop report summarizes recent advances in MCL biology and treatment, including BTKi and CAR-T, and outlines key research priorities to overcome resistance and clinical heterogeneity for future progress.

This preclinical study identifies that the miR-17-92 cluster suppresses the tumor suppressor BTG2, leading to B-cell receptor signaling overactivation and suggesting BTG2 as a prognostic biomarker.

The deubiquitinase USP35 stabilizes CXCR3 protein expression in MCL cells, promoting oncogenic signaling via JAK/STAT and c-Myc, identifying the USP35-CXCR3 axis as a novel therapeutic target.

Upregulation of the mTOR pathway drives acquired resistance to PRMT5 inhibitors in preclinical MCL models; combining with an mTOR inhibitor like temsirolimus overcomes this resistance and improves survival.