BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models

Xiaohong Zhao, Yuan Ren, Matthew Lawlor, Bijal D. Shah, Paul M.C. Park, Tint Lwin, Xuefeng Wang, Kenian Liu, Michelle Wang, Jing Gao, Tao Li, Mousheng Xu, Ariosto S. Silva, Kaplan Lee, Tinghu Zhang, John M. Koomen, Huijuan Jiang, Praneeth R. Sudalagunta, Mark B. Meads, Fengdong ChengChengfeng Bi, Kai Fu, Huitao Fan, William S. Dalton, Lynn C. Moscinski, Kenneth H. Shain, Eduardo M. Sotomayor, Gang Greg Wang, Nathanael S. Gray, John L. Cleveland, Jun Qi, Jianguo Tao

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Zhao et al. show that resistance to the BCL-2 inhibitor ABT-199 is conferred by super enhancer reprogramming and loss of BCL2 amplicons in models of mantle cell lymphoma and double hit lymphoma. Combining ABT-199 with the CDK7 inhibitor THZ1 prevents or reverses BCL-2 inhibitor resistance.

Original languageEnglish (US)
Pages (from-to)752-766.e9
JournalCancer Cell
Volume35
Issue number5
DOIs
StatePublished - May 13 2019

    Fingerprint

Keywords

  • ABT-199
  • BCL2
  • CDK7
  • THZ1
  • double-hit lymphoma
  • drug persister
  • drug resistance
  • mantle cell lymphoma
  • super-enhancer remodeling
  • transcriptome reprogramming

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Zhao, X., Ren, Y., Lawlor, M., Shah, B. D., Park, P. M. C., Lwin, T., Wang, X., Liu, K., Wang, M., Gao, J., Li, T., Xu, M., Silva, A. S., Lee, K., Zhang, T., Koomen, J. M., Jiang, H., Sudalagunta, P. R., Meads, M. B., ... Tao, J. (2019). BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models. Cancer Cell, 35(5), 752-766.e9. https://doi.org/10.1016/j.ccell.2019.04.005