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Leuk Lymphoma. 2010 Jul;51(7):1315-25. doi: 10.3109/10428194.2010.483299.

CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system.

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1
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

CD38 is an ecto-enzyme that hydrolyzes NAD. Its expression is a prognostic marker for chronic lymphocytic leukemia. We have characterized individual variation in CD38 expression in lymphoblastoid cell lines from 288 healthy subjects of three ethnicities. Expression varied widely, with significant differences among ethnic groups, and was correlated significantly with CD38 enzymatic activity and protein levels. The CD38 gene was then resequenced using DNA from the same cell lines, with the identification of 53 single nucleotide polymorphisms (SNPs) and one indel, 39 novel. One SNP, rs1130169, was significantly associated with CD38 mRNA expression and explained a portion of the difference in expression among ethnic groups. EMS assay showed nuclear protein binding at or near this SNP. We also determined that variation in CD38 expression in these cell lines was associated with variation in antineoplastic drug sensitivity. These results represent a step toward understanding mechanisms involved in CD38 expression.

PMID:
20470215
PMCID:
PMC2892000
DOI:
10.3109/10428194.2010.483299
[Indexed for MEDLINE]
Free PMC Article
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