Fludarabine induces differential expression of proteins in human leukemia and lymphoma cells.
The purine analog fludarabine (FdAMP) is widely used for chemotherapy of B-lymphoid malignancies, and multiple mechanisms of action leading to apoptosis have been proposed. We examined changes at the protein level induced in the Raji cell line (Burkitt's lymphoma) by fludarabine nucleoside (FdA). Raji cells are sensitive to FdA. Raji cells treated with FdA (3 micro M, 24 hours), accumulate multiple phosphorylated forms of p53 in the nucleus that in turn degrade to phosphorylated forms of p40. Using CD antibody microarrays to determine surface expression profiles for Raji cells treated with FdA, we found up-regulation of the following CD antigens: CD20, CD54, CD80, CD86, and CD95. FdA thus induces changes in the genetic program of the cells that might be exploited to obtain synergy with therapeutic antibodies.
Henrich
S
S
School of Molecular and Microbial Biosciences, University of Sydney, New South Wales, Australia.
Gez
S
S
Crossett
B
B
Mulligan
S P
SP
Christopherson
R I
RI
D000818:Animals; D000906:Antibodies / Q000378:metabolism / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000906:Antibodies; D015703:Antigens, CD; D016159:Tumor Suppressor Protein p53; D014740:Vidarabine; C024352:fludarabine