Genetic events in the pathogenesis of multiple myeloma

Abstract

The genetics of myeloma has been increasingly elucidated in recent years. Recurrent genetic events, and also biologically distinct and clinically relevant genetic subtypes of myeloma have been defined. This has facilitated our understanding of the molecular pathogenesis of the disease. In addition, some genetic abnormalities have proved to be highly reproducible prognostic factors. With the expanding therapeutic armamentarium, it is time to include genetic assessment as part of clinical evaluation of myeloma patients to guide management. In this review we examine the role of various genetic abnormalities in the molecular pathogenesis of myeloma, and the use of such abnormalities in disease classification, prognosis and clinical management.

DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7

“…1 It is characterized by clonal proliferation of long-lived plasma cells associated with the overproduction of monoclonal immunoglobulin. 2 The main clinical manifestations of the disease include anemia, recurrent infections, renal failure, and osteolytic lesions, which lead to devastating complications for the patients and their quality of life.…”

MafB oncoprotein detected by immunohistochemistry as a highly sensitive and specific marker for the prognostic unfavorable t(14;20) (q32;q12) in multiple myeloma patients

“…2 As a result, we only found protein expression of MafB confined to t(14;20)-positive patients. This is remarkable, as primary translocations involving MafB and CMaf are grouped together according their expression and correlation of high CYCLIN D2 activity and poor prognosis in MM (reviewed in Chng et al 3 ).…”

Transcriptional repression by the HDAC4–RelB–p52 complex regulates multiple myeloma survival and growth

“…M ultiple Myeloma (MM) is a monoclonal tumour of plasma cells (PCs) that develops from post germinalcenter (GC) B cells 1,2 . While MM tumours have been classified into different genetic subgroups based on several genetic abnormalities [1][2][3][4][5][6][7] , several of them are divided into three distinct groups of chromosomal translocations involving (1) Cyclin D (2) MAF and (3) MMSET/FGFR3 genes 2 .…”

“…While MM tumours have been classified into different genetic subgroups based on several genetic abnormalities [1][2][3][4][5][6][7] , several of them are divided into three distinct groups of chromosomal translocations involving (1) Cyclin D (2) MAF and (3) MMSET/FGFR3 genes 2 . To develop novel therapeutic approaches to target all the genetic subgroups of MM, it is important to identify the molecular requirements and the survival signals that are common to all genetic subgroups of MM tumours.…”

“…To develop novel therapeutic approaches to target all the genetic subgroups of MM, it is important to identify the molecular requirements and the survival signals that are common to all genetic subgroups of MM tumours. Among the genetic abnormalities found in MM, activating mutations of the RAS and BRAF pathway, dysregulation of the myc gene and activating mutations in the NF-kB pathway have been frequently observed 2,6 . Of these, the NF-kB pathway is of particular significance in the pathogenesis of MM because NF-kB not only provides survival and proliferation signals to the MM tumours but also promotes the release of several cytokines that further enhance tumour growth.…”