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Hindawi, Bone Marrow Research, (2018), p. 1-9, 2018

DOI: 10.1155/2018/5742954

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BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death

Journal article published in 2018 by Helen J. S. Stewart ORCID, Sabah Chaudry, Asante Crichlow, Freya Luiling Feilding, Timothy J. T. Chevassut ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of S100A8 and S100A9 mRNA and protein in a reversible manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML cell death. Daunorubicin alone causes a dose- and time-dependent increase in S100A8 and S100A9 protein levels in AML cell lines which is overcome by cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in causing apoptosis via suppression of S100A8 and S100A9 levels.