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

Mark Wroblewski, Marina Scheller-Wendorff, Florian Udonta, Raimund Bauer, Jara Schlichting, Lin Zhao, Isabel Ben Batalla, Victoria Gensch, Sarina Päsler, Lei Wu, Marek Wanior, Hanna Taipaleenmäki, Simona Bolamperti, Zeynab Najafova, Klaus Pantel, Carsten Bokemeyer, Jun Qi, Eric Hesse, Stefan Knapp, Steven JohnsenSonja Loges

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)939-948
Number of pages10
JournalHaematologica
Volume103
Issue number6
DOIs
StatePublished - Jun 3 2018

ASJC Scopus subject areas

  • Hematology

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    Wroblewski, M., Scheller-Wendorff, M., Udonta, F., Bauer, R., Schlichting, J., Zhao, L., Batalla, I. B., Gensch, V., Päsler, S., Wu, L., Wanior, M., Taipaleenmäki, H., Bolamperti, S., Najafova, Z., Pantel, K., Bokemeyer, C., Qi, J., Hesse, E., Knapp, S., ... Loges, S. (2018). BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of hematopoietic stem cells. Haematologica, 103(6), 939-948. https://doi.org/10.3324/haematol.2017.181354