title: CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system.
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.
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Hartman
authors.forename: Linda L
authors.initials: LL
authors.lastname: Pelleymounter
authors.forename: Irene
authors.initials: I
authors.lastname: Moon
authors.forename: Krishna
authors.initials: K
authors.lastname: Kalari
authors.forename: Mohan
authors.initials: M
authors.lastname: Liu
authors.forename: Tse-Yu
authors.initials: TY
authors.lastname: Wu
authors.forename: Carlos
authors.initials: C
authors.lastname: Escande
authors.forename: Veronica
authors.initials: V
authors.lastname: Nin
authors.forename: Eduardo N
authors.initials: EN
authors.lastname: Chini
authors.forename: Richard M
authors.initials: RM
authors.lastname: Weinshilboum
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics* / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D012333:RNA, Messenger; D003561:Cytarabine; D003841:Deoxycytidine; D051997:ADP-ribosyl Cyclase 1; D000093542:Gemcitabine
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