| Literature DB >> 19657367 |
B G M Durie1, 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.
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 Gsk3beta. SNP signatures were linked to the number of bone lesions, log(2) DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: EPHX1 (P=0.0026); log(2) DKK-1 expression (P=0.0046); serum lactic dehydrogenase (LDH) (P=0.0074); Gsk3beta (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.Entities:
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Year: 2009 PMID： 19657367 PMCID： PMC3684359 DOI： 10.1038/leu.2009.129
Source DB: PubMed Journal: Leukemia ISSN： 0887-6924 Impact factor: 11.528