THE CD2-SCL TRANSGENE ALTERS THE PHENOTYPE AND FREQUENCY OF T-LYMPHOMAS IN N-RAS TRANSGENIC OR P53 DEFICIENT MICE

Abnormal expression of SCL (TAL-1/TCL5) occurs in the majority of paed iatric cases of acute T-cell lymphoblastic leukemia (T-ALL), Unexpecte dly however, transgenic mice carrying scl coupled to the human T-cell specific CD2 enhancer (CD2-scl) did not spontaneously develop T-cell l ymphomas despite high levels of scl expression in their thymocytes, An alogous to other transgenic models of lymphomagenesis, it is likely th at 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 r elapsed 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-r as 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 nu llizygous mice, shifted the pattern of organ involvement to the periph eral lymphoid organs, In contrast, CD2-scl transgene expression accele rated lymphomagenesis in p53 heterozygous mice, These data suggest tha t the collaborative effects of scl with N-ras or p53 vary according to the developmental stage of the T-cell.