Open AccessEvidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells
Author(s) -
Eric Cholez,
Véronique Debuysscher,
Jérôme Bourgeais,
Cédric Boudot,
Jérôme Leprince,
François Tron,
Bertrand Brassart,
Aline Régnier,
E Bissac,
Emmanuel Pecnard,
Fabrice Gouilleux,
Kaı̈ss Lassoued,
Valérie Gouilleux-Gruart
Publication year - 2012
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/leu.2012.112
Subject(s) - oxidative stress , glutathione , apoptosis , transcription factor , biology , reactive oxygen species , microbiology and biotechnology , stat5 , chemistry , genetics , gene , biochemistry , signal transduction , enzyme
STAT5 transcription factors are involved in normal B lymphocyte development and in leukemogenesis. We show that the inhibition of STAT5A expression or activity in the NALM6, 697 and Reh leukemic pre-B cell lines, results in a higher spontaneous apoptosis and an increased FAS-induced cell death. However, the molecular mechanisms underlying the altered pre-B cell survival are unclear. We used a proteomic approach to identify proteins that are differentially regulated in cells expressing (NALM6Δ5A) or not a dominant negative form of STAT5A. Among the 14 proteins identified, six were involved in the control of the oxidative stress like glutathione (GSH) synthetase and DJ-1. Accordingly, we showed increased levels of reactive oxygen species (ROS) in NALM6Δ5A cells and suppression of the increased sensitivity to Fas-mediated apoptosis by the GSH tripeptide. Similar results were observed when NALM6 cells were treated with TAT-STAT5Δ5A fusion proteins or STAT5A shRNA. In addition, the 697 and Reh pre-B cells were found to share number of molecular changes observed in NALM6Δ5A cells including ROS generation, following inhibition of STAT5 expression or function. Our results point out to a hitherto undescribed link between STAT5 and oxidative stress and provide new insights into STAT5 functions and their roles in leukemogenesis.