A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling.

Abstract:

:Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas. We previously demonstrated the oncogenic potential of Stat5, with thymic lymphoblastic lymphomas developing in a significant proportion of transgenic (TG) mice overexpressing Stat5a or Stat5b in lymphocytes. In addition, immunization or expression of a T-cell receptor (TCR) transgene augmented the rate of tumor formation. Here, we investigate the mechanism of Stat5-mediated lymphomagenesis by exploring the contributions of major histocompatibility complex (MHC)/TCR and pre-TCR signals. We present data demonstrating that Stat5b TG mice unexpectedly develop CD8(+) lymphoma even in the absence of either pre-TCR signaling or normal thymic selection. Indeed, acceleration of Stat5b transgene-mediated lymphoma occurred on TCRalpha(-/-) and pre-TCRalpha(-/-) backgrounds. In light of these data, we propose a model in which alterations in T-cell development at the double-negative/double-positive (DN/DP) stages cooperate with cytokine-mediated pathways in immature thymocytes to give rise to lymphoblastic T-cell lymphomas in Stat5b TG mice.

journal_name

Blood

journal_title

Blood

authors

Bessette K,Lang ML,Fava RA,Grundy M,Heinen J,Horne L,Spolski R,Al-Shami A,Morse HC 3rd,Leonard WJ,Kelly JA

doi

10.1182/blood-2007-04-084707

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

344-50

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2007-04-084707

journal_volume

111

pub_type

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