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Neutral tumor evolution in myeloma is associated with poor prognosis

Lookup NU author(s): Professor Graham Jackson


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© 2017 by The American Society of Hematology. Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory drug (IMiD) therapy. By analyzing mutant allele frequency distributions in tumors, we found that 17% to 20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in nonintensively treated patients, which is consistent with the reduced therapeutic efficacy of microenvironment-modulating IMiDs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcomes and personalizing therapy.

Publication metadata

Author(s): Johnson DC, Lenive O, Mitchell J, Jackson G, Owen R, Drayson M, Cook G, Jones JR, Pawlyn C, Davies FE, Walker BA, Wardell C, Gregory WM, Cairns D, Morgan GJ, Houlston RS, Kaiser MF

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2017

Volume: 130

Issue: 14

Pages: 1639-1643

Print publication date: 05/10/2017

Online publication date: 21/08/2017

Acceptance date: 07/08/2017

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2016-11-750612

PubMed id: 28827410


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