Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia. Academic Article uri icon

Overview

abstract

  • The TEL-JAK2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. TEL-JAK2 transgenic expression in the mouse lymphoid lineage results in fatal and rapid T-cell leukemia/lymphoma. In the present report we show that T-cell leukemic cells from EmuSRalpha-TEL-JAK2 transgenic mice present an aberrant CD8(+) differentiation phenotype, as determined by the expression of stage-specific cell surface markers and lineage-specific genes. TEL-JAK2 transforms immature CD4(-)CD8(-) double-negative thymocytes, as demonstrated by the development of T-cell leukemia with full penetrance in a Rag2-deficient genetic background. This disease is similar to the bona fide TEL-JAK2 disease as assessed by phenotypic and gene profiling analyses. Pre-TCR signaling synergizes with TEL-JAK2 to transform immature thymocytes and initiate leukemogenesis as shown by (1) the delayed leukemia onset in Rag2-, CD3epsilon- and pTalpha-deficient mice, (2) the occurrence of recurrent chromosomal alterations in pre-TCR-deficient leukemia, and (3) the correction of delayed leukemia onset in Rag2-deficient TEL-JAK2 mice by an H-Y TCRalphabeta transgene that mimics pre-TCR signaling. Although not affecting leukemia incidence and mouse survival, TCRalphabeta expression was shown to facilitate leukemic cell expansion in secondary lymphoid organs.

publication date

  • December 27, 2006

Research

keywords

  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Leukemia, T-Cell
  • Oncogene Proteins, Fusion
  • Receptors, Antigen, T-Cell, alpha-beta

Identity

Scopus Document Identifier

  • 34247326918

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-09-048801

PubMed ID

  • 17192390

Additional Document Info

volume

  • 109

issue

  • 9