BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

Journal Article · Fri Dec 07 04:00:00 EST 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.10.112· OSTI ID:22210349

Goupille, Olivier ^[1]; Penglong, Tipparat ^[1]; Lefevre, Carine; Granger, Marine; Kadri, Zahra ^[1]; Fucharoen, Suthat ^[2]; Maouche-Chretien, Leila ^[1]; Leboulch, Philippe ^[1]; Chretien, Stany ^[1]

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1. CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France)
2. Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand)

Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

• OSTI ID: 22210349
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1-2 Vol. 429; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD CELLS
CELL PROLIFERATION
DRUGS
ERYTHROPOIESIS
ERYTHROPOIETIN
INHIBITION