As proof of concept, we identified a low micromolar potency molecule (compound 30666) that inhibited immunoglobulin production by MM cells and blocked expression of an array of IgH translocation-induced oncogenes (CCND1, FGFR3/MMSET, and MYC) in MM and NHL cell lines.
DNA was extracted from archival CPs of B-cell NHL cases with previous fluorescence in situ hybridization (FISH) assays for MYC rearrangement and/or IGH/BCL-2 translocation.
Detection of cryptic and variant IGH-MYC rearrangements in high-grade non-Hodgkin's lymphoma by fluorescence in situ hybridization: implications for cytogenetic testing.
It is unusual to find both t(14;18) and C-MYC translocation in the same tumour; those cases in which it has been described include examples of high-grade B-cell NHL (either de novo or transformed FL) or B-cell acute lymphoblastic lymphoma.
Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
These results indicate an IGL-mediated rearrangement of an unknown gene at 9q34 that together with BCL2 and MYC might be involved in the lymphomagenesis of the present case of FCCL and perhaps in other cases of non-Hodgkin lymphoma in which t(9;22) is sporadically occurring.
Interestingly these fragile sites were located in the same chromosomal bands as the oncogenes, MOS, MYC, BCL-1 and BCL-2 as well as cancer breakpoints specifically associated with non-Hodgkin's lymphoma, suggesting the possibility that fragile sites may play a critical role in the pathogenesis of non-Hodgkin's lymphoma.
In a non-Hodgkin's lymphoma that contains a translocated c-myc gene this enhancer is retained on the 14q+ chromosome and occurs within sequences shown to activate previously cryptic promoters of the c-myc gene.
In a non-Hodgkin lymphoma, Manca, harboring a t(8; 14) translocation, c-myc gene is broken within intron 1, and its exons 2 and 3 are translocated to a site between the heavy chain joining region cluster and C mu-coding DNA segment of the immunoglobulin heavy chain locus.