TCA cycle mode switch determines the fate of pirtobrutinib-tolerant persister cells in mantle cell lymphoma.

ABSTRACT:

Abstract

Bruton tyrosine kinase inhibitors (BTKis) and cell therapy have successfully been used to treat mantle cell lymphoma (MCL). However, therapy resistance inevitably emerges. Cancer cells can progressively develop stable resistance by traversing through a transient drug-tolerant persister (DTP) state. The mechanisms enabling DTP cells to reversibly adapt to therapies and evolve to acquire heterogeneity remain poorly understood, and characterizing DTP cells in MCL continues to pose a challenge for clinic translation. Here, using pirtobrutinib, a recently US Food and Drug Administration-approved noncovalent BTKi, we identified pirtobrutinib-tolerant persister cells exhibiting morphological variability by presenting a unique population of enlarged cells (giant cells) with revers

SUBMITTER: Wang W 

PROVIDER: S-EPMC12824699 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature