CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system.
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.
Hartman
William R
WR
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Pelleymounter
Linda L
LL
Moon
Irene
I
Kalari
Krishna
K
Liu
Mohan
M
Wu
Tse-Yu
TY
Escande
Carlos
C
Nin
Veronica
V
Chini
Eduardo N
EN
Weinshilboum
Richard M
RM
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
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D012333:RNA, Messenger; D003561:Cytarabine; D003841:Deoxycytidine; D051997:ADP-ribosyl Cyclase 1; D000093542:Gemcitabine
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