Bcr-abl translocation can occur during the induction of multidrug resistance and confers apoptosis resistance on myeloid leukemic cell lines

被引:19
作者
Belloc, F
Cotteret, S
Labroille, G
Schmit, V
Jaloustre, C
Dumain, P
Durrieu, F
Reiffers, J
Boisseau, MR
Bernard, P
Lacombe, F
机构
[1] HOP HAUT LEVEQUE,HEMATOL LAB,F-33604 PESSAC,FRANCE
[2] UNIV VICTOR SEGALEN,HEMATOL LAB,F-33076 BORDEAUX,FRANCE
[3] UNIV BORDEAUX 2,CNRS,UMR 5540,F-33000 BORDEAUX,FRANCE
关键词
apoptosis; bcr-abl translocation; leukemia; multidrug resistance;
D O I
10.1038/sj.cdd.4400303
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Apoptosis was studied in parental and Mdr-1 expressing U937, HL60 and K562 myeloid leukemic cell lines using mdr unrelated inducers of apoptosis such as Ara-C, cycloheximide, serum deprivation, ceramide, monensin and UV irradiation, Apoptosis was efficiently induced by all these treatments In U937 and HL60 cells while K562 cells exhibited an apoptosis resistant phenotype except with UV acid monensin, The pattern of apoptosis resistance in mds-1 expressing U937 (U987-DR) and HL60 (HL60-DR100) was similar to that presented by K562. This apoptosis resistant phenotype of mdr cells was not overcome by concentrations of verapamil inhibiting the P-gp 170 pump. The acquisition of this phenotype was posterior to the mdr-1 expressing phenotype since a HL60-DR5 variant, selected at the beginning of the induction of resistance, presented a low level of mdr-1 expression without resistance to apoptosis. The variations observed in the Fas (CD95) expression between sensitive and resistant cells were not sufficient to account for apoptosis resistance, However, a high expression in Abl antigen was found in all the apoptosis-resistant cells, RT-PCR and Western blot analysis showed that this increase in Abl antigen content was accompanied by the expression in U937-DR and HL60-DR100 cells of a hybrid bcr/abl mRNA and a 210 kD Bcr/Abl protein which was constitutive in M562. This expression was due to the translocation of abl and the amplification of the bcr-abl translocated gene, These results are in agreement with the role of Bcr/Abl tyrosine protein kinase as sin inhibitor of apoptosis independently of the mdr-1 expression, They also suggest that translocation of the abl gene in the bcr region is a highly probable rearrangement in the mdr-1 expressing myeloid cells and that Bcr/Abl tyrosine kinase effect on apoptosis needs the regulation of intracellular pH and is inactive against UV-induced apoptosis.
引用
收藏
页码:806 / 814
页数:9
相关论文
共 29 条
  • [1] BARRY MA, 1993, CANCER RES, V53, P2349
  • [2] A FLOW CYTOMETRIC METHOD USING HOECHST-33342 AND PROPIDIUM IODIDE FOR SIMULTANEOUS CELL-CYCLE ANALYSIS AND APOPTOSIS DETERMINATION IN UNFIXED CELLS
    BELLOC, F
    DUMAIN, P
    BOISSEAU, MR
    JALLOUSTRE, C
    REIFFERS, J
    BERNARD, P
    LACOMBE, F
    [J]. CYTOMETRY, 1994, 17 (01): : 59 - 65
  • [3] BILHOUNABERA C, 1992, LEUKEMIA, V6, P595
  • [4] FLOW CYTOMETRIC STUDY OF IDARUBICIN AND DAUNORUBICIN ACCUMULATION AND THE EFFECT OF VERAPAMIL IN LEUKEMIC-CELL LINES AND FRESH CELLS FROM PATIENTS WITH ACUTE NONLYMPHOBLASTIC LEUKEMIA
    BOIRON, JM
    BELLOC, F
    MONTASTRUC, M
    CONYMAKHOUL, P
    DUMAIN, P
    MARIT, G
    MAHON, FX
    PUNTOUS, M
    LOPEZ, F
    LACOMBE, F
    REIFFERS, J
    [J]. LEUKEMIA RESEARCH, 1994, 18 (05) : 313 - 318
  • [5] CERAMIDE SYNTHASE MEDIATES DAUNORUBICIN-INDUCED APOPTOSIS - AN ALTERNATIVE MECHANISM FOR GENERATING DEATH SIGNALS
    BOSE, R
    VERHEIJ, M
    HAIMOVITZFRIEDMAN, A
    SCOTTO, K
    FUKS, Z
    KOLESNICK, R
    [J]. CELL, 1995, 82 (03) : 405 - 414
  • [6] CAMPOS L, 1993, BLOOD, V81, P3091
  • [7] CHAPMAN RS, 1995, MOL PHARMACOL, V48, P334
  • [8] EXPRESSION OF P53 PROTEIN DURING THE CELL-CYCLE MEASURED BY FLOW-CYTOMETRY IN HUMAN LEUKEMIA
    DANOVA, M
    GIORDANO, M
    MAZZINI, G
    RICCARDI, A
    [J]. LEUKEMIA RESEARCH, 1990, 14 (05) : 417 - 422
  • [9] Durrieu F., 1996, British Journal of Haematology, V93, P342
  • [10] PLEIOTROPIC DRUG-RESISTANCE AND SURVIVAL ADVANTAGE IN LEUKEMIC-CELLS WITH DIMINISHED APOPTOTIC RESPONSE
    FRANKFURT, OS
    SECKINGER, D
    SUGARBAKER, EV
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1994, 59 (02) : 217 - 224