scl, a gene frequently activated in human T cell leukaemia, does not induce lymphomas in transgenic mice.
The scl gene is implicated in human T cell acute lymphoblastic leukaemia (T-ALL) through its involvement in the t(1;14)(p32;q11) chromosomal translocation and, more frequently, as a result of a tumour-specific interstitial deletion on chromosome 1. The consequence of both these chromosomal alterations is overexpression of scl in the leukaemic cells. Despite the strong inference of a role in human T-ALL, scl has not yet been demonstrated to be causally involved in neoplastic transformation. We attempted to do this by generating transgenic mice in which scl expression was directed to the T cell lineage using the CD2 enhancer and the strong SR alpha viral promoter (CD2-scl mice). Three transgenic lines, all of which expressed the scl transgene at a high level, were bred and analysed. No alterations in T cell development were seen in the mice. Unexpectedly CD2-scl mice did not develop tumours, nor did the transgene enhance tumourigenesis by Moloney murine leukaemia virus. These findings throw into question the mechanism by which aberrant scl expression contributes to T cell leukaemogenesis.
Robb
L
L
Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Victoria, Australia.
Rasko
J E
JE
Bath
M L
ML
Strasser
A
A
Begley
C G
CG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D018801:CD2 Antigens / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000166:cytology; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D018801:CD2 Antigens; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human