In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues -: correlation with clinical course

被引:28
作者
Bromidge, TJ
Turner, DL
Howe, DJ
Johnson, SA
Rule, SAJ
机构
[1] Taunton & Somerset Hosp, Leukaemia Res Unit, Taunton TA1 5DA, Somerset, England
[2] Taunton & Somerset Hosp, Dept Haematol, Taunton TA1 5DA, Somerset, England
关键词
chronic lymphocytic leukaemia; in vitro chemosensitivity; purine analogue therapy;
D O I
10.1038/sj.leu.2401095
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 Po 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.
引用
收藏
页码:1230 / 1235
页数:6
相关论文
共 29 条
  • [1] BINET JL, 1981, CANCER-AM CANCER SOC, V48, P198, DOI 10.1002/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO
  • [2] 2-V
  • [3] Bosanquet AG, 1996, BLOOD, V87, P1962
  • [4] ADAPTATION OF THE TDT ASSAY FOR SEMIQUANTITATIVE FLOW CYTOMETRIC DETECTION OF DNA STRAND BREAKS
    BROMIDGE, TJ
    HOWE, DJ
    JOHNSON, SA
    PHILLIPS, MJ
    [J]. CYTOMETRY, 1995, 20 (03): : 257 - 260
  • [5] National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment
    Cheson, BD
    Bennett, JM
    Grever, M
    Kay, N
    Keating, MJ
    OBrien, S
    Rai, KR
    [J]. BLOOD, 1996, 87 (12) : 4990 - 4997
  • [6] COLLINS RJ, 1989, BRIT J HAEMATOL, V71, P343
  • [7] DELANNOY A, 1993, NEW ENGL J MED, V328, P812
  • [8] P53 GENE DELETION PREDICTS FOR POOR SURVIVAL AND NONRESPONSE TO THERAPY WITH PURINE ANALOGS IN CHRONIC B-CELL LEUKEMIAS
    DOHNER, H
    FISCHER, K
    BENTZ, M
    HANSEN, K
    BENNER, A
    CABOT, G
    DIEHL, D
    SCHLENK, R
    COY, J
    STILGENBAUER, S
    VOLKMANN, M
    GALLE, PR
    POUSTKA, A
    HUNSTEIN, W
    LICHTER, P
    [J]. BLOOD, 1995, 85 (06) : 1580 - 1589
  • [9] FLUDARABINE INHIBITS DNA-REPLICATION - A RATIONALE FOR ITS USE IN THE TREATMENT OF ACUTE LEUKEMIAS
    GANDHI, V
    HUANG, P
    PLUNKETT, W
    [J]. LEUKEMIA & LYMPHOMA, 1994, 14 : 3 - 9
  • [10] GORCZYCA W, 1993, CANCER RES, V53, P1945