INTERACTION OF ABL AND RAF WITH IL-7 SIGNALING PATHWAY AND TRANSFORMATION OF PRE-B CELLS FROM RESISTANT MICE

After in vivo inoculation with abl/myc- and raf/myc-containing retrovi ruses, BALB/c mice predominantly develop late stage B cell tumors (pla smacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strain s. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly for m in vivo pre-B lymphomas in both mouse strains, Mechanisms mediating loss of IL-7 dependence are different depending on whether the I nf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signalin g is constitutively active in abl/myc induced pre-B cell tumors, In co ntrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformat ion or loss of IL-7 dependence.