title: Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells.
abstract: 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.
authors.affiliation: Department of Immunology, Inserm U925, Université Picardie Jules Verne, CHU Amiens, Amiens, France.
authors.forename: E
authors.initials: E
authors.lastname: Cholez
authors.forename: V
authors.initials: V
authors.lastname: Debuysscher
authors.forename: J
authors.initials: J
authors.lastname: Bourgeais
authors.forename: C
authors.initials: C
authors.lastname: Boudot
authors.forename: J
authors.initials: J
authors.lastname: Leprince
authors.forename: F
authors.initials: F
authors.lastname: Tron
authors.forename: B
authors.initials: B
authors.lastname: Brassart
authors.forename: A
authors.initials: A
authors.lastname: Regnier
authors.forename: E
authors.initials: E
authors.lastname: Bissac
authors.forename: E
authors.initials: E
authors.lastname: Pecnard
authors.forename: F
authors.initials: F
authors.lastname: Gouilleux
authors.forename: K
authors.initials: K
authors.lastname: Lassoued
authors.forename: V
authors.initials: V
authors.lastname: Gouilleux-Gruart
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism*; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000502:physiology*
chemical_list: D050799:STAT5 Transcription Factor