Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG.
The human PVT-1 gene is located on chromosome 8 telomeric to the c-Myc gene and it is frequently involved in the translocations occurring in variant Burkitt's lymphomas and murine plasmacytomas.
Since the IgH switch recombination and somatic hypermutation mechanism are turned off in plasma cells and plasma cell tumors, the MYC rearrangements are thought to be mediated by unknown mechanisms that contribute to structural genomic instability in all kinds of tumors.
This report implicates an unidentified role of Bcl-X(L) in bone marrow plasma cell tumor formation, as ABL-MYC retroviral infection only elicits bone marrow plasma cell tumors in mice that ectopically express Bcl-X(L) in their B- and plasma cells.
We conclude that Myc(His) insertion into Igh predictably induces B-cell and plasma-cell tumors in mice, providing a valuable mouse model for understanding the transformation-inducing consequences of the MYC/Myc-activating endemic Burkitt lymphoma t(8;14)/plasmacytoma T(12;15) translocation.
Based on these observations, we speculate that the c-myc protein may upregulate expression of translocated c-myc in mouse plasmacytomas possibly via an USF-binding E-box motif in the IgH 3' enhancer.
The amino-terminal phosphorylation sites of C-MYC are frequently mutated in Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas.
The rearrangement places the 3' C alpha enhancer (3' alpha E) greater than 200 kb downstream of the c-myc promoters, however c-myc mRNA levels are similar to those observed in plasmacytomas with typical T(12;15)s that translocate 3' alpha E much closer (15-25 kb) and upstream of c-myc.
This study investigated the expression of c-myc and 2 other members of the myc gene family, L- and N-myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma--multiple myeloma (MM).
We previously identified a plasmacytoma-specific protein which binds to the c-myc promoter region 290 base pairs 5' of the P1 transcription start site.
The plasmacytoma-specific occurrence of this protein suggests that it may play a role in the transcriptional repression of the normal c-myc gene observed in plasmacytomas.
This interpretation is also supported by the finding that the expression of the c-myc genes of lymphoblastoid cells and of HL-60 promyelocytic leukemia cells are repressed when they are transferred into a mouse plasmacytoma background.
Nevertheless, the myc polypeptide produced in the plasmacytoma is probably the same as that from the intact c-myc gene because the exon lost by breakage and translocation is non-coding.
NIARD-associated chromosome translocations occurred 1.3-2 kilobases (kb) 5' of the mouse c-myc gene where NIARD recombines with the switch region of the C(alpha) immunoglobulin gene in various murine plasmacytomas.