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

William R Hartman1, Linda L Pelleymounter, Irene Moon

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

Leukemia & Lymphoma
|May 18, 2010
PubMed
Summary

Individual variation in CD38 expression, a marker for chronic lymphocytic leukemia, was studied in 288 healthy individuals. A specific SNP, rs1130169, was linked to CD38 mRNA levels and ethnic differences, impacting drug sensitivity.

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Area of Science:

  • Biochemistry
  • Genetics
  • Immunology

Background:

  • CD38 is an ecto-enzyme crucial in NAD metabolism.
  • CD38 expression serves as a prognostic indicator in chronic lymphocytic leukemia.
  • Understanding CD38 expression variability is vital for disease management.

Purpose of the Study:

  • To characterize individual and ethnic variations in CD38 expression.
  • To identify genetic factors influencing CD38 expression.
  • To explore the link between CD38 expression and antineoplastic drug sensitivity.

Main Methods:

  • Analysis of CD38 expression in lymphoblastoid cell lines from 288 individuals across three ethnicities.
  • Whole-gene sequencing of CD38 to identify single nucleotide polymorphisms (SNPs) and indels.
  • Electrophoretic Mobility Shift Assay (EMSA) to assess protein binding to identified SNPs.
  • Correlation analysis between CD38 expression, genetic variations, and drug sensitivity.

Main Results:

  • Significant variations in CD38 expression were observed among ethnic groups.
  • Fifty-three SNPs and one indel were identified in the CD38 gene, with 39 being novel.
  • SNP rs1130169 showed a significant association with CD38 mRNA expression and ethnic group differences.
  • Nuclear protein binding was detected at or near rs1130169.
  • CD38 expression levels correlated with sensitivity to antineoplastic drugs.

Conclusions:

  • Genetic variations, particularly SNP rs1130169, contribute to CD38 expression variability and ethnic differences.
  • CD38 expression influences cellular response to chemotherapy drugs.
  • These findings provide insights into the genetic underpinnings of CD38 regulation and its clinical relevance.