title: The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice.
abstract: Abnormal expression of SCL (TAL-1/TCL5) occurs in the majority of paediatric cases of acute T-cell lymphoblastic leukemia (T-ALL). Unexpectedly however, transgenic mice carrying scl coupled to the human T-cell specific CD2 enhancer (CD2-scl) did not spontaneously develop T-cell lymphomas despite high levels of scl expression in their thymocytes. Analogous to other transgenic models of lymphomagenesis, it is likely that additional genetic abnormalities are required to cooperate with scl to trigger lymphomagenesis. Two possible candidates are the p53 and N-ras genes which are mutated in some cases of T-ALL, particularly in relapsed disease. Therefore, we examined lymphomagenesis in the progeny of CD2-scl mice crossed with N-ras transgenic mice or p53 deficient. Surprisingly, the frequency of lymphomas in the p53 nullizygous or N-ras transgenic mice was not enhanced by expression of the scl transgene. In fact, expression of scl in both genetic backgrounds paradoxically reduced the frequency of thymic lymphomas and, at least in the p53 nullizygous mice, shifted the pattern of organ involvement to the peripheral lymphoid organs. In contrast, CD2-scl transgene expression accelerated lymphomagenesis in p53 heterozygous mice. These data suggest that the collaborative effects of scl with N-ras or p53 vary according to the developmental stage of the T-cell.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Curtis
authors.forename: L
authors.initials: L
authors.lastname: Robb
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.forename: C G
authors.initials: CG
authors.lastname: Begley
mesh_terms: D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D018801:CD2 Antigens / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002999:Clone Cells; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D011905:Genes, ras; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D016399:Lymphoma, T-Cell / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D013953:Thymus Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics*
chemical_list: 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; D016159:Tumor Suppressor Protein p53; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human