| First Author | dos Santos NR | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 9 | Pages | 3972-81 |
| PubMed ID | 17192390 | Mgi Jnum | J:121496 |
| Mgi Id | MGI:3710284 | Doi | 10.1182/blood-2006-09-048801 |
| Citation | dos Santos NR, et al. (2007) Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia. Blood 109(9):3972-81 |
| abstractText | 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. |
