Diverse karyotypic abnormalities of the c -myc locus associated with c -myc dysregulation and tumor progression in multiple myeloma

Chromosome translocations in multiple myeloma

“…Translocations of 8q24 in MM are complex, and appear to be late events involved in the progression of the disease (Shou et al, 2000). This is in surprising contrast to their role as a primary event in Burkitt's lymphoma and mouse plasmacytoma.…”

“…Through a combination of conventional cytogenetics, SKY analyses, metaphase FISH analyses, isolation of molecular clones, and RT ± PCR assays Chesi et al, 1997Chesi et al, , 1998aGabrea et al, 1999;Shaughnessy et al, 2001;Shou et al, 2000;, unpublished results), we have identi®ed at least one IgH translocation in 36/39 (92%) MM cell lines examined, with at least 17/39 (44%) lines having two or more di erent IgH translocations, and at least 5/39 (13%) lines having three or more di erent IgH translocations. In preliminary metaphase FISH analyses using¯anking IgL probes, we identi®ed Igl translocations in 7/30 (23%) MM cell lines, but no Igk translocation in the 21 MM cell lines examined (Martelli, 2001, unpublished results).…”

“…Despite the similarity in phenotype of human MM and murine plasmacytoma tumors, earlier studies identi®ed t(8;14) translocations, c-myc DNA rearrangements, or c-myc ampli®cation in less than 10% of MM tumors and cell lines (Calasanz et al, 1997;Dewald et al, 1985;Lai et al, 1995;Nishida et al, 1997;Sawyer et al, 1995). Recently, however, it was determined that one c-myc allele is expressed selectively in all twelve informative MM cell lines that have polymorphic mutations that distinguish mRNA expressed from the maternal and paternal c-myc alleles (Shou et al, 2000;Kuehl, 2001, unpublished). This result suggested cis-dysregulation of c-myc in all MM cell lines, and prompted a more sensitive molecular cytogenetic analysis of MM cell lines and tumors.…”

Bone morphogenetic proteins induce apoptosis in multiple myeloma cells by Smad-dependent repression of MYC

“…7 Overexpression of MYC occurs by different mechanisms including gene amplification, translocation and mutation. MYC chromosomal rearrangements are present in many myeloma cell lines, 8,9 and to a varying degree (15--46%) in primary myeloma cells. 10,11 Moreover, 40% of MYC translocations in human myeloma cell lines do not involve an immunoglobulin gene.…”

Understanding the multiple biological aspects leading to myeloma

“…66,67 The gene typically deregulated by such events is MYC, the deregulation of which may lead to a more aggressive disease phase 68 but such events still occur in 21% of myelomas at presentation and involve the sequestration of active enhancer elements, resulting in increased expression of MYC (BA Walker et al submitted manuscript, 2014). Interestingly, transgenic mice engineered to over-express MYC in late B cells also develop myeloma.…”