BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells

Haematologica. 2018 Jun;103(6):939-948. doi: 10.3324/haematol.2017.181354. Epub 2018 Mar 22.


Although inhibitors of bromodomain and extra terminal domain (BET) proteins show promising clinical activity in different hematologic malignancies, a systematic analysis of the consequences of pharmacological BET inhibition on healthy hematopoietic (stem) cells is urgently needed. We found that JQ1 treatment decreases the numbers of pre-, immature and mature B cells while numbers of early pro-B cells remain constant. In addition, JQ1 treatment increases apoptosis in T cells, all together leading to reduced cellularity in thymus, bone marrow and spleen. Furthermore, JQ1 induces proliferation of long-term hematopoietic stem cells, thereby increasing stem cell numbers. Due to increased numbers, JQ1-treated hematopoietic stem cells engrafted better after stem cell transplantation and repopulated the hematopoietic system significantly faster after sublethal myeloablation. As quantity and functionality of hematopoietic stem cells determine the duration of life-threatening myelosuppression, BET inhibition might benefit patients in myelosuppressive conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Azepines / pharmacology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Biomarkers
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Self Renewal / drug effects*
  • Graft Survival / drug effects
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / radiation effects
  • Immunophenotyping
  • Mice
  • Phenotype
  • Proteins / antagonists & inhibitors*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Triazoles / pharmacology*


  • (+)-JQ1 compound
  • Antineoplastic Agents
  • Azepines
  • Biomarkers
  • Proteins
  • Triazoles
  • bromodomain and extra-terminal domain protein, human