A potential role for centrosomal deregulation within IgH translocation-positive myeloma.
Multiple myeloma is a late stage B-cell malignancy that is characterized by recurrent translocations into the immunoglobulin heavy chain locus as well as multiple and complex chromosomal abnormalities. Multiple myeloma is not characterized by a defining IgH translocation partner locus; rather, the frequency of individual translocations ranges from 5% to 15% of the patient population. The current hypothesis that IgH translocations contribute to chromosomal instability through the augmented expression of cyclin D family members and upstream regulatory gene products has led to the development of clinical therapies targeting these potentially oncogenic gene products. Here, we postulate that IgH translocations affect both cyclin D family members and spindle assembly pathways. In forming the hypothesis, this manuscript provides a mechanistic connectivity between IgH translocations and associated chromosome 13 deletions and highlights a number of additional gene products that, along with already defined target genes, may be deregulated in myeloma and represent potential therapeutic targets.
Maxwell
Christopher A
CA
Department of Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Pilarski
Linda M
LM
D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009194:Myeloma Proteins / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics*
D056741:Cyclin D; D016213:Cyclins; D007143:Immunoglobulin Heavy Chains; D009194:Myeloma Proteins