Overexpression of v-abl uniquely cooperates with c-myc dysregulation in induction of plasma cell tumors, bypassing the need for T-lymphocytic help and overcoming T-lymphocytic interference

Abstract

We have investigated the effects of T lymphocytes on induction of mouse plasma cell tumors. We show that ABL-MYC, a plasmacytomagenic retrovirus that constitutively expresses v-abl and c-myc, is able to induce plasmacytomas in 100% of athymic BALB/c mice, with or without intraperitoneal pristane pretreatment. Other induction regimens are ineffective under these conditions, indicating that the combination of v-abl and c-myc oncogenes is uniquely able to transform plasma cells in mice that are deficient in T lymphocytes. Furthermore, in the absence of pristane, ABL-MYC-infected athymic congenics developed plasmacytomas in half the time required for euthymic BALB/c mice, suggesting that T lymphocytes can have a negative effect and can retard, but not totally inhibit, the outgrowth of plasmacytomas. This phenomenon could not be appreciated in other regimens of plasmacytoma induction, because only ABL-MYC is sufficient to induce plasmacytomas in athymic mice or in euthymic mice in the absence of pristane pretreatment.

Insertion of Myc into Igh Accelerates Peritoneal Plasmacytomas in Mice

“…Furthermore, it strengthened our contention that absent the ability to predictably induce T(12;15) translocations in mouse B cells and plasma cells (28), the insertion of Myc into the Igh locus of gene-targeted mice provides a good solution to mimicking this translocation in a manner conducive to plasmacytoma development (15). + T-cell help (33), an essential cofactor for normal isotype switching (34) and peritoneal plasmacytomagenesis in C mice (35). Among the various mouse strains carrying Myc transgenes driven by immunoglobulin enhancers (36)(37)(38)(39)(40)(41), none has been reported thus far to induce plasma cell neoplasms as the predominant tumor type.…”

Neoplastic development in plasma cells

“…These PCTs developed in mesenteric and peripheral lymph nodes in 70% of the mice. There was a striking difference in the mean latent periods between BALB/cAn and BALB/cAn nu/nu mice, which were 79 and 30 days, respectively, suggesting to the authors that T cells had an inhibiting effect on PCT development (70). The ABL/MYC, virus has proven to be an effective means for inducing monoclonal antibodies.…”

Lymph nodes and Peyer's patches of IL-6 transgenic BALB/c mice harbor T(12;15) translocated plasma cells that contain illegitimate exchanges between the immunoglobulin heavy-chain μ locus and c-myc

“…Second, it does not require pre-treatment (priming) with pristane, ie Abl/Mycinduced plasmacytomas can develop independently from the artificial microenvironment of the inflammatory granuloma. Indeed, some tumors have been reported to originate in lymph nodes, 30 the tissues where the 5Ј-C /c-myc + clones were found in the IL-6 transgenic BALB/c mice. Third, the Abl/Myc virus is the only plasmacytomagenic agent that has been demonstrated to override the apparent block of plasmacytoma development in BALB/c.IL-6 −/− mice.…”