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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4220-4228. Prepublished online as a Blood First Edition Paper on January 18, 2007; DOI 10.1182/blood-2006-08-044370. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-08-044370v1 109/10/4220    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bourdeau, A. Articles by Tremblay, M. L Search for Related Content PubMed PubMed Citation Articles by Bourdeau, A. Articles by Tremblay, M. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 30, 2006 Accepted January 10, 2007 TC-PTP-deficient bone marrow stromal cells fail to support normal B lymphopoiesis due to abnormal secretion of interferon- Annie Bourdeau, Nadia Dube, Krista M Heinonen, Jean-Francois Theberge, Karen M Doody, and Michel L Tremblay* McGill Cancer Center, McGill University, Montreal, Canada Department of Biochemistry, McGill University, Montreal, Canada Division of Experimental Medicine, McGill University, Montreal, Canada * Corresponding author; email: michel.tremblay{at}mcgill.ca. The T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of the Jak/Stat cytokine signaling pathway. Our study shows that the absence of TC-PTP leads to an early bone marrow B cell deficiency characterized by hindered transition from the pre-B cell to immature B cell stage. This phenotype is intrinsic to the B cells but most importantly due to bone marrow stroma abnormalities. We found that bone marrow stromal cells from TC-PTP-/- mice have the unique property of secreting 232-890 pg/ml of IFN-. These high levels of IFN-, result in 2-fold reduction in mitotic index upon IL-7 stimulation of TC-PTP-/- pre-B cells and lower responsiveness of IL-7 receptor downstream Jak/Stat signaling molecules. Moreover, we noted constitutive phosphorylation of Stat1 in those pre-B cells and demonstrated that this was due to soluble IFN- secreted by TC-PTP-/- bone marrow stromal cells. Interestingly, culturing murine early pre-B leukemic cells within a TC-PTP deficient bone marrow stroma environment leads to a 40% increase in apoptosis in these malignant cells. Our results unraveled a new role for TC-PTP in normal B lymphopoiesis and suggest that modulation of bone marrow microenvironment is a potential therapeutic approach for selected B cell leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. M. Heinonen, A. Bourdeau, K. M. Doody, and M. L. Tremblay Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-{gamma} signaling PNAS, June 9, 2009; 106(23): 9368 - 9372. [Abstract] [Full Text] [PDF] S.-W. Lee, S. Salek-Ardakani, R. S. Mittler, and M. Croft Hypercostimulation through 4-1BB Distorts Homeostasis of Immune Cells J. Immunol., June 1, 2009; 182(11): 6753 - 6762. [Abstract] [Full Text] [PDF] F. Moore, M. L. Colli, M. Cnop, M. I. Esteve, A. K. Cardozo, D. A. Cunha, M. Bugliani, P. Marchetti, and D. L. Eizirik PTPN2, a Candidate Gene for Type 1 Diabetes, Modulates Interferon-{gamma}-Induced Pancreatic {beta}-Cell Apoptosis Diabetes, June 1, 2009; 58(6): 1283 - 1291. [Abstract] [Full Text] [PDF] A. Wakeel, J. A. Kuriakose, and J. W. McBride An Ehrlichia chaffeensis Tandem Repeat Protein Interacts with Multiple Host Targets Involved in Cell Signaling, Transcriptional Regulation, and Vesicle Trafficking Infect. Immun., May 1, 2009; 77(5): 1734 - 1745. [Abstract] [Full Text] [PDF]

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