The Genetic Architecture of Multiple Myeloma

Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ failure. Recent evidence has revealed my...

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Main Authors: Steven M. Prideaux, Emma Conway O'Brien, Timothy J. Chevassut
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Advances in Hematology
Online Access:http://dx.doi.org/10.1155/2014/864058
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author Steven M. Prideaux
Emma Conway O'Brien
Timothy J. Chevassut
author_facet Steven M. Prideaux
Emma Conway O'Brien
Timothy J. Chevassut
author_sort Steven M. Prideaux
collection DOAJ
description Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ failure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined subtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between hyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations of the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of which being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic events that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations, mutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis.
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spelling doaj-art-373f5786f47e4b42bfeda4ea08bd13552025-08-20T02:07:41ZengWileyAdvances in Hematology1687-91041687-91122014-01-01201410.1155/2014/864058864058The Genetic Architecture of Multiple MyelomaSteven M. Prideaux0Emma Conway O'Brien1Timothy J. Chevassut2Brighton and Sussex Medical School, Sussex University, Falmer, Brighton BN1 9PS, UKBrighton and Sussex Medical School, Sussex University, Falmer, Brighton BN1 9PS, UKBrighton and Sussex Medical School, Sussex University, Falmer, Brighton BN1 9PS, UKMultiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ failure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined subtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between hyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations of the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of which being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic events that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations, mutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis.http://dx.doi.org/10.1155/2014/864058
spellingShingle Steven M. Prideaux
Emma Conway O'Brien
Timothy J. Chevassut
The Genetic Architecture of Multiple Myeloma
Advances in Hematology
title The Genetic Architecture of Multiple Myeloma
title_full The Genetic Architecture of Multiple Myeloma
title_fullStr The Genetic Architecture of Multiple Myeloma
title_full_unstemmed The Genetic Architecture of Multiple Myeloma
title_short The Genetic Architecture of Multiple Myeloma
title_sort genetic architecture of multiple myeloma
url http://dx.doi.org/10.1155/2014/864058
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