HMGB1: an important regulator of myeloid differentiation and acute myeloid leukemia as well as a promising therapeutic target

• DOI: 10.1007/s00109-020-01998-5
• Publication Date: 2020-10-31T16:02:46Z
• Authors: Lulu Liu; Jingjing Zhang; Xianning Zhang; Panpan Cheng; Lei Liu; Qian Huang; Haihui Liu; Saisai Ren; Peng Wei; Cuiling Wang; Cuiyun Dou; Lulu Chen; Xin Liu; Hao Zhang; Mingtai Chen
• Keywords: TGFBI; HMGB1; Histone deacetylase inhibitor

Abstract High mobility group box 1 (HMGB1) is a non-histone nuclear protein which has been intensively studied in various physiological and pathological processes including leukemia. Here this study, we further demonstrated that HMGB1 presents higher expression the bone marrow mononuclear cells of acute myeloid leukemia (AML) patients compared with normal controls contributes to AML pathogenesis progression by inhibiting apoptosis, facilitating proliferation, inducing differentiation blockade cells. Mechanistic investigation revealed transforming growth factor beta-induced (TGFBI) acts as potential downstream target lentivirus-mediated knockdown TGFBI impaired phorbol-12-myristate-13-acetate (PMA) all-trans retinoic acid (ATRA)–induced cell lines. On other hand, chidamide, an orally histone deacetylase inhibitor, decreases significantly concomitant upregulation expression, confers therapeutic effect on differentiation, apoptosis proliferation. In conclusion, our findings provide additional insights promising AML, also present experimental evidence for clinical application chidamide novel agent therapy downregulating expression. Key messages induces proliferation inhibits HMGB1. Chidamide, selective HDAC via