We showed tetraspanins attenuated peIF4E and its targets [c‑Myc, cyclin D1 (cycD1)]; eIF4E attenuation was Akt-dependent. eIF4E inhibition in MM cells [bone marrow (BM), lines] by siRNA and/or the anti‑viral drug and competitive eIF4E inhibitor ribavirin (RBV) deleteriously affected MM cells in a similar manner to the overexpression of tetraspanins.
Nearly half of these tumors are nonhyperdiploid and mostly have immunoglobulin H (IgH) translocations that involve 5 recurrent chromosomal loci, including 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (fibroblast growth factor receptor 3 [FGFR3] and multiple myeloma SET domain [MMSET]), 16q23 (c-maf), and 20q11 (mafB).
Both methods were applied to isolate VH genes from murine B cell lymphoma (A20 and BCL1), myeloma (NS1) and hybridoma (SP6) cell lines and from freshly isolated human chronic lymphocytic leukemia and lymphoma cells.
This suggests to us that cyclin D1 deregulation due to the presence of t(11;14) is involved in the early development of plasma cell neoplasms, and that this event alone is not enough for the development of symptomatic myeloma.
14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM.
IL-2-dependent clones established from the DN alphabeta T cell population in the PEC of IL-2 receptor alpha-chain transgenic B6 mice exhibited potent cytotoxicity against a series of B cell lineage leukemias and myelomas, such as CD5+BCL1 and MOPC, without affecting NK-susceptible targets.
Simultaneous translocations of FGFR3/MMSET and CCND1 into two different IGH alleles in multiple myeloma: lack of concurrent activation of both proto-oncogenes.
Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms.
Furthermore, gene expression profiling enabled the identification of putative translocations causing dysregulation of CCND1 (1 MM and 1 PCL) and MAFB (1 MM and 1 PCL) without any apparent involvement of immunoglobulin loci.
In patient 1, the clonal plasma cells harbored IgH translocations (14q32); however, FISH with probes for the four most frequent IgH partner genes in MM (CCND1, FGFR3, MAF, and MYC) did not detect translocations involving any of them.
We applied ND and MM-MSCs 72h secretomes to MM cell lines (U266 and ARP-1) for 12-72h and then assayed the cells' (viability, cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α).
The study aim was to investigate Stat 3 activation in a series of multiple myeloma (MM) cases and its effect on downstream targets such as the anti-apoptotic proteins Bcl-xL, Mcl-1, and Bcl-2, and the cell-cycle protein cyclin D1.Forty-eight cases of MM were analyzed.
To test the tumorigenic potential of cyclin D1b in vivo, we generated cell clones derived from the non-CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a.