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Coexistent hyperdiploidy does not abrogate poor prognosis in myeloma with adverse cytogenetics and may precede IGH translocations

Lookup NU author(s): Professor Graham Jackson

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Abstract

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.

Publication metadata

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

Journal: Blood

Year: 2015

Volume: 125

Issue: 5

Pages: 831-840

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

URL: http://dx.doi.org/10.1182/blood-2014-07-584268

DOI: 10.1182/blood-2014-07-584268

PubMed id: 25428216

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