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Lookup NU author(s): Professor Graham Jackson
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The acquisition of the cytogenetic abnormalities hyperdiploidy or translocations into the immunoglobulin gene loci are considered as initiating events in the pathogenesis of myeloma and were often assumed to be mutually exclusive. These lesions have clinical significance; hyperdiploidy or the presence of the t(11; 14) translocation is associated with a favorable outcome, whereas t(4; 14), t(14; 16), and t(14; 20) are unfavorable. Poor outcomes are magnified when lesions occur in association with other high-risk features, del17p and +1q. Some patients have coexistence of both good and poor prognostic lesions, and there has been no consensus on their risk status. To address this, we have investigated their clinical impact using cases in the Myeloma IX study (ISRCTN68454111) and shown that the coexistence of hyperdiploidy or t(11; 14) does not abrogate the poor prognosis associated with adverse molecular lesions, including translocations. We have also used single-cell analysis to study cases with coexistent translocations and hyperdiploidy to determine how these lesions cosegregate within the clonal substructure, and we have demonstrated that hyperdiploidy may precede IGH translocation in a proportion of patients. These findings have important clinical and biological implications, as we conclude patients with coexistence of adverse lesions and hyperdiploidy should be considered high risk and treated accordingly.
Author(s): Pawlyn C, Melchor L, Murison A, Wardell CP, Brioli A, Boyle EM, Kaiser MF, Walker BA, Begum DB, Dahir NB, Proszek P, Gregory WM, Drayson MT, Jackson GH, Ross FM, Davies FE, Morgan GJ
Publication type: Article
Publication status: Published
Print publication date: 29/01/2015
Online publication date: 26/11/2014
Acceptance date: 09/11/2014
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
PubMed id: 25428216
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