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

William R. Hartman, Linda L. Pelleymounter, Irene Moon, Krishna Kalari, Mohan Liu, Tse Yu Wu, Carlos Escande, Veronica Nin, Eduardo N. Chini, Richard M. Weinshilboum

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalLeukemia and Lymphoma
Volume51
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • CD38
  • NAD
  • SNPs
  • expression variation
  • gene expression
  • mRNA expression
  • microarray
  • polymorphism
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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