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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2517-2525. Prepublished online as a Blood First Edition Paper on January 13, 2009; DOI 10.1182/blood-2008-07-169110. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2008-07-169110v1 113/11/2517    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kim, D. H. Articles by Lipton, J. H. Search for Related Content PubMed PubMed Citation Articles by Kim, D. H. Articles by Lipton, J. H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 21, 2008 Accepted December 8, 2008 Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia Dong Hwan Kim*, Wei Xu, Clement Ma, Xiangdong Liu, Katherine Siminovitch, Hans A. Messner, and Jeffrey H. Lipton Chronic Myelogenous Leukemia Group, Department of Hematology/Medical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada Department of Biostatistics, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, Canada Analytical Genetics Technology Centre, University Health Network, Toronto, ON, Canada * Corresponding author; email: drkiim{at}medimail.co.kr. Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, characterized by the presence of BCR/ABL fusion gene. It is unclear which cellular events drive BCR/ABL gene translocation or initiate leukemogenesis in CML. Bcl-2 promotes survival of hematopoietic stem cells. Accordingly, apoptosis-related pathway may involve in the leukemogenesis of CML. In the current study, we evaluated 80 SNP markers involved in the pathways of apoptosis (n=30), angiogenesis (n=7), myeloid cell growth (n=14), xenobiotic metabolism (n=13), WT1 signaling (n=7), interferon signaling (n=4) and others (n=5) in 170 CML patients and 182 healthy controls. In a single marker analysis, following SNPs were identified including VEGFA, BCL2, CASP7, JAK3, CSF3 and HOCT1. In the multivariate logistic model with these 9 SNPs and covariates, only BCL2 (rs1801018) was significantly associated with the susceptibility to CML (p=0.05; adjusted-OR 2.16, [1.00-4.68]). In haplotype analyses, haplotype block of BCL2 consistently showed significant association with the susceptibility to CML. Risk allele analysis showed that a greater number of risk alleles from BCL2 SNP correlated to increasing risk of CML (overall p=0.1, OR 1.84, [1.06-3.22] for 3-4 risk alleles vs. 0-1 risk alleles). The current study indicated that BCL2 SNP seemed to be associated with increasing susceptibility to CML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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