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 containing retroviruses is facilitated by T cells and completely dependent on IL-6. To determine whether kinases with differing specificities reflect alternative biochemical pathways in B cell tumorigenesis, we have employed an abl/ myc containing retrovirus to assess neoplastic development. In contrast with raf/ myc, abl/ myc disease is T cell and IL-6 independent. An examination of the IL-6 signal transduction pathway reveals that this pathway, as defined by activation of Stat3, is inducible by IL-6 in raf/ myc tumors but constitutively activated in abl/ myc tumors. These findings provide a mechanism for the derivation of cytokine-independent plasma cell tumors and suggest that both IL-6-dependent and independent tumors may arise in vivo depending on the particular mutational events incurred during tumorigenesis.