title: Molecular pathogenesis of multiple myeloma: basic and clinical updates.
abstract: Multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21, and lacks recurrent immunoglobulin gene translocations. Non-hyperdiploid myeloma in contrast is characterized by chromosome translocations t(4;14), t(14;16), t(14;20), t(6;14) and t(11;14). A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin D gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression of a MAF family transcription factor, or indirectly by as yet unidentified mechanisms. Secondary genetic events include rearrangements of MYC, activating mutations of NRAS, KRAS or BRAF, a promiscuous array of mutations that activate NFkB and deletions of 17p. Among the poor-risk genetic features are t(4;14), t(14;16), t(14;20), del 17p and gains of 1q. Available evidence supports the use of a risk-stratified approach to the treatment of patients with multiple myeloma, with the early and prolonged use of bortezomib particularly in patients with t(4;14) and del 17p.
authors: Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA.
authors: Marta
authors: M
authors: Chesi
authors: P Leif
authors: PL
authors: Bergsagel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D049109:Cell Proliferation; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D056741:Cyclin D / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D015994:Incidence; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D011719:Pyrazines / Q000627:therapeutic use; D012307:Risk Factors; D012737:Sex Factors; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D015996:Survival Rate; D014178:Translocation, Genetic; D014314:Trisomy; D014481:United States / Q000453:epidemiology; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D056741:Cyclin D; D007075:Immunoglobulin M; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D011719:Pyrazines; D000069286:Bortezomib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins