Genome-wide CRISPR screening uncovers potential targets and mechanisms of vincristine resistance in DLBCL

Br J Haematol. 2023 Aug;202(4):720-721. doi: 10.1111/bjh.18900. Epub 2023 May 31.

Abstract

In this issue, Rovsing et al. employ unbiased genome-wide CRISPR screening and functional cellular assays to investigate the cellular response to vincristine, an important component of the front-line DLBCL treatment R-CHOP. Their findings reveal intriguing targets and mechanisms that hold promise for enhancing DLBCL treatment and provide a foundation for the development of future drug regimens. This research prompts further exploration of the translational potential to advance more effective and individualized approaches in the clinical management of DLBCL. Commentary on: Rovsing et al. Resistance to vincristine in DLBCL by disruption of p53-induced cell cycle arrest and apoptosis mediated by KIF18B and USP28. Br J Haematol 2023;202:825-839.

Keywords: CRISPR; R-CHOP; diffuse large B-cell lymphoma; p53; resistance; vincristine.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Humans
  • Kinesins
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Prednisone / therapeutic use
  • Rituximab / therapeutic use
  • Treatment Outcome
  • Ubiquitin Thiolesterase
  • Vincristine / pharmacology
  • Vincristine / therapeutic use

Substances

  • Vincristine
  • Cyclophosphamide
  • Rituximab
  • Doxorubicin
  • Prednisone
  • USP28 protein, human
  • Ubiquitin Thiolesterase
  • KIF18B protein, human
  • Kinesins