DISTINCT TUMORIGENIC POTENTIAL OF ABL AND RAF IN B-CELL NEOPLASIA - ABL ACTIVATES THE IL-6 SIGNALING PATHWAY

The development of murine plasma cell tumors induced by raf/myc contai ning retroviruses is facilitated by T cells and completely dependent o n IL-6. To determine whether kinases with differing specificities refl ect alternative biochemical pathways in B cell tumorigenesis, we have employed an abl/myc containing retrovirus to assess neoplastic develop ment. In contrast with raf/myc, abl/myc disease is T cell and IL-6 ind ependent. An examination of the IL-6 signal transduction pathway revea ls that this pathway, as defined by activation of Stat3, is inducible by IL-6 in raf/myc tumors but constitutively activated in abl/myc tumo rs. These findings provide a mechanism for the derivation of cytokine- independent plasma cell tumors and suggest that both IL-6-dependent an d independent tumors may arise in vivo depending on the particular mut ational events incurred during tumorigenesis.