Durie, B. G. M., Van Ness, B., Ramos, C., Stephens, O., Haznadar, M., Hoering, A., Haessler, J., Katz, M. S., Mundy, G. R., Kyle, R. A., Morgan, G. J., Crowley, J., Barlogie, B., Shaughnessy Jr., J. (2009) Genetic polymorphisms of EPHX1, Gsk3 beta, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma. LEUKEMIA, 23 (10). pp. 1913-1919. ISSN 0887-6924

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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 Gsk3 beta. 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); Gsk3 beta (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. Leukemia (2009) 23, 1913-1919; doi: 10.1038/leu.2009.129; published online 6 August 2009

Item Type:	Article
Authors (ICR Faculty only):	Morgan, Gareth
All Authors:	Durie, B. G. M., Van Ness, B., Ramos, C., Stephens, O., Haznadar, M., Hoering, A., Haessler, J., Katz, M. S., Mundy, G. R., Kyle, R. A., Morgan, G. J., Crowley, J., Barlogie, B., Shaughnessy Jr., J.
Uncontrolled Keywords:	myeloma; bone disease; SNP; molecular; prognosis;BODY-MASS INDEX; GROWTH-FACTOR-I; MULTIPLE-MYELOMA; EPOXIDE HYDROLASE; RECEPTOR GENE; WNT; SURVIVAL; OSTEOBLASTS; INHIBITION; PATHWAY
Funding Acknowledgement:	International Myeloma Foundation ; National Cancer Institute [CA32102, CA38926, CA21115, CA97513]
Funding Text:	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 CA97513 (JDS and BB).
Research teams:	ICR divisions > Clinical Studies > Molecular Haematology (including Cytogenetics Group and Cell Markers) ICR divisions > Molecular Pathology > Molecular Haematology (including Cytogenetics Group and Cell Markers) Clinical Units > Haemato-Oncology Unit
Depositing User:	Users 10 not found.
Date Deposited:	02 Nov 2009 10:32
Last Modified:	10 Feb 2010 11:52
URI:	http://publications.icr.ac.uk/id/eprint/8940

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