MCL Literature Feed

This review details diverse BTKi resistance mechanisms beyond BTK mutations, providing a framework for developing next-generation inhibitors and combination strategies to overcome treatment failure in MCL.

Single-cell RNA sequencing reveals pre-existing, minor therapy-resistant subclones at diagnosis, which are selected during treatment, explaining early relapse and highlighting cell-cycle dysregulation as a common resistance mechanism.

PRMT5 inhibition sensitizes MCL cells to ferroptosis by disrupting the ATF5-SLC7A11 axis, providing a rationale for combining PRMT5 inhibitors with ferroptosis inducers for relapsed/refractory disease.

Single-cell multi-omics reveals genetic and non-genetic pirtobrutinib resistance mechanisms in MCL, identifying the cohesin complex as a potential target to restore drug sensitivity.

Genomic analysis reveals MCL relapse is driven by the expansion of pre-existing resistant subclones, not new mutations, highlighting the need for deep sequencing at diagnosis to prevent recurrence.

Preclinical data suggests PRMT5 inhibition is a promising combination therapy strategy for high-risk MCL with ATM and TP53 mutations, which are known to confer therapeutic resistance.

Mitochondrial ACSS1 enables nutrient-stressed B-cell lymphomas to produce DNA/RNA building blocks via acetate metabolism, identifying ACSS1 as a novel therapeutic target to overcome metabolic adaptation.

This review contextualizes MCL-approved BTK inhibitors by summarizing their distinct covalent and non-covalent binding mechanisms, which underlie differences in efficacy, toxicity, and overcoming resistance.

This comprehensive review synthesizes emerging biomarkers beyond standard prognosticators, including MRD, ctDNA, and advanced imaging, to better guide personalized treatment in the targeted therapy era.

The lymph node microenvironment silences the pro-apoptotic protein BIM via a CD40/PI3K/FOXO1 axis, driving broad drug resistance that can be overcome by bispecific T-cell engager immunotherapy.

A novel single-cell technique, LiP-Seq, identified IFITM2 upregulation in rare persistent MCL cells post-CAR-T, revealing a new mechanism of immune evasion and a potential therapeutic target.

Absence of CD38 expression in conventional nodal MCL strongly correlates with TP53 inactivation and a distinct genetic profile, identifying a high-risk subgroup via routine flow cytometry.

Dual inhibition of anti-apoptotic proteins BIRC5 and MCL-1 is a novel preclinical strategy to overcome drug resistance in mantle cell lymphoma, offering a potential new therapeutic avenue.

The NAMPT inhibitor KPT-9274 sensitizes TP53-mutated MCL to alkylating chemotherapy by disrupting the DNA damage response, offering a novel combination strategy for this high-risk, chemo-resistant population.

A novel preclinical compound dually inhibiting FLT3 and HDAC is developed, introducing a new potential therapeutic mechanism for hematologic malignancies, though its specific relevance to MCL is unknown.

A novel liquid biopsy technique using cell-free chromatin profiling non-invasively tracks disease origin and monitors therapy response, offering a powerful new tool for MRD and biomarker discovery.

This longitudinal study reveals MCL acquires new high-risk genetic features after chemoimmunotherapy, explaining relapse and emphasizing the need for genomic profiling to guide subsequent therapies.

This paper details a new UPLC-MS/MS method for rapid venetoclax plasma quantification, which could facilitate therapeutic drug monitoring to optimize dosing and toxicity management in MCL.

The HSP90-MYC-CDK9 molecular network is identified as a key driver of therapeutic resistance in MCL, suggesting HSP90 or CDK9 inhibitors as potential strategies to overcome it.

This report summarizes the 2025 LRF MCL Workshop, highlighting key research developments in pathogenesis, resistance, and novel therapies, thereby setting the agenda for future clinical and translational research.

This review positions CAR-T and bispecific antibodies as complementary tools for relapsed/refractory MCL, advocating for individualized sequencing and combinations to optimize outcomes in heavily pretreated, high-risk patients.

Real-world data from an Italian compassionate use program confirms pirtobrutinib's efficacy in heavily pre-treated, relapsed/refractory MCL, including patients who have failed prior covalent BTK inhibitors.

This review outlines the historical evolution in understanding transformed mantle cell lymphoma, highlighting changes in its pathological diagnosis, genomic drivers, and the clinical challenges it presents.

This preclinical development of an optimized CXCR4-targeting theranostic pair offers a novel strategy to simultaneously image and treat MCL by targeting a key pathway in aggressive disease.

In a real-world French cohort, MCL patients failing CAR-T therapy have dismal outcomes (median OS 5.8 months), highlighting an urgent need for effective salvage, with bispecific antibodies showing promise.

This review outlines the evolution of BTK inhibitors, highlighting how non-covalent agents like pirtobrutinib overcome C481-mediated resistance, extending the therapeutic sequence for relapsed/refractory MCL.

A matching-adjusted indirect comparison suggests pirtobrutinib improves survival versus standard of care for relapsed/refractory MCL patients who have progressed on a prior covalent BTKi, supporting its use.

This review summarizes mechanisms of resistance and relapse after CAR-T/CAR-NK therapy, such as antigen loss and T-cell exhaustion, offering insights for improving durability in MCL.

This case report demonstrates CD19 downregulation as a key mechanism of resistance and subsequent relapse in a heavily pretreated MCL patient following initially effective CD19-targeted CAR-T therapy.

This preclinical study shows a SOX11 inhibitor overcomes BTKi, BCL2i, and CAR-T resistance by targeting the PAX5/CD19 axis, a novel upstream BCR signaling mechanism.