Genetic polymorphisms of EPHX1, Gsk3β, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma

B. G.M. Durie, B. Van Ness, C. Ramos, O. Stephens, M. Haznadar, A. Hoering, J. Haessler, M. S. Katz, G. R. Mundy, R. A. Kyle, G. J. Morgan, J. Crowley, B. Barlogie, J. Shaughnessy

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing 3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3β. SNP signatures were linked to the number of bone lesions, log2 DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: EPHX1 (P=0.0026); log2 DKK-1 expression (P=0.0046); serum lactic dehydrogenase (LDH) (P=0.0074); Gsk3β (P=0.02) and TNFSF8 (P=0.04) were linked to bone disease. This assessment of genetic polymorphisms identifies SNPs with both potential biological relevance and utility in prognostic models of myeloma bone disease.

Original languageEnglish (US)
Pages (from-to)1913-1919
Number of pages7
JournalLeukemia
Volume23
Issue number10
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This investigation was supported in part by an unrestricted grant from the International Myeloma Foundation (Bank on a Cure project), as well as by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102 and CA38926 (SWOG); and CA21115 (ECOG); plus CA 97513 (JDS and BB).

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