In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues--correlation with clinical course.
Samples from 51 chronic lymphocytic leukaemia (CLL) patients (42 typical, nine atypical) were assessed for in vitro response to fludarabine and cladribine (2-CdA) using the flow cytometric terminal deoxynucleotidyl transferase (TdT) assay. No difference was demonstrated between the in vitro response of typical and atypical CLL and previous treatment did not result in a more apoptosis resistant phenotype. The assay could not distinguish those patients who required subsequent treatment from those whose disease remained stable, and universal cross-resistance/sensitivity to the two purine analogues was demonstrated. The assay's potential for use in the rapid assessment of in vivo response to purine analogue therapy in CLL was limited; correctly predicting the clinical outcome of 10/12 patients to treatment but failing to predict progression in two p53 deficient patients. The level of bcl-2 in the clonal lymphocytes did not influence the in vitro, spontaneous or drug-induced, apoptosis.
Leukaemia Research Unit, Taunton and Somerset Hospital, UK.
T J
TJ
Bromidge
D L
DL
Turner
D J
DJ
Howe
S A
SA
Johnson
S A
SA
Rule
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D017338:Cladribine / Q000627:therapeutic use*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017338:Cladribine; D004253:DNA Nucleotidylexotransferase; D014740:Vidarabine; C024352:fludarabine