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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.
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https://hal-univ-tours.archives-ouvertes.fr/hal-02425419
Contributor : Valérie Gouilleux <>
Submitted on : Monday, December 30, 2019 - 2:45:40 PM
Last modification on : Friday, January 10, 2020 - 4:12:18 PM

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E Cholez, V Debuysscher, J Bourgeais, C. Boudot, J. Leprince, et al.. Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells. Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2012, 26 (11), pp.2390-2397. ⟨10.1038/leu.2012.112⟩. ⟨hal-02425419⟩

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