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Updated: May 9, 2026

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms

B S Wyspiańska1, A J Bannister1, I Barbieri1

  • 1Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, UK.

Leukemia
|August 10, 2013
PubMed

Insights

I-BET151 inhibits BET proteins, showing therapeutic potential for leukemia. This specific inhibitor downregulates LMO2, offering a promising alternative treatment for myeloproliferative neoplasms driven by JAK2 kinase.

Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • BET protein inhibition shows therapeutic benefits in preclinical leukemia models.
  • Mixed lineage leukemia (MLL) fusion proteins drive certain leukemias.
  • BET proteins bind acetylated lysines in histones.

Purpose of the Study:

  • To investigate the efficacy of I-BET151, a BET family bromodomain inhibitor, in erythroleukemic cells and polycythemia vera patient precursors.
  • To explore the role of LMO2 downregulation by I-BET151.
  • To examine the relationship between I-BET151 and Janus kinase 2 (JAK2) signaling in HEL cells.

Main Methods:

  • Treatment of human erythroleukemic (HEL) cell line and primary erythroid precursors with I-BET151.
  • Gene expression analysis to identify genes downregulated by I-BET151.
  • Comparison of transcriptional changes induced by I-BET151 and a JAK2 inhibitor (TG101209).
  • Generation and testing of JAK2 inhibitor-resistant HEL cells.

Main Results:

  • I-BET151 inhibited growth in HEL cells and erythroid precursors from polycythemia vera patients.
  • LMO2, an oncogenic regulator, was significantly downregulated by I-BET151.
  • Transcriptional changes induced by I-BET151 and TG101209 showed significant overlap.
  • JAK2 inhibitor-resistant HEL cells remained sensitive to I-BET151.

Conclusions:

  • I-BET151 demonstrates growth inhibitory effects in erythroleukemic models.
  • The findings suggest a common pathway of action involving JAK2 and BET inhibition.
  • I-BET151 represents a potential therapeutic strategy for myeloproliferative neoplasms driven by active JAK2 kinase.

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