Failure to detect the P-glycoprotein multidrug resistant phenotype in cases of resistant childhood acute lymphocytic leukaemia

Ubezio, Paolo; Limonta, Margherita; D’Incalci, Maurizio; Damia, Giovanna; G, Masera; Giudici, Giovanni; Wolverton, Judith S.; Beck, William T.

doi:10.1016/0277-5379(89)90367-2

Cited by 26 publications

(9 citation statements)

References 6 publications

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“…PIO, P50 and P90 represent the 10th, 50th ( = median) and 90th percentiles of LC50 values of the group of initial ALL patients, given in jig ml1' (except for L-Asparaginase which is in U ml-'). (Tawa et al, 1990;Rothenberg et al, 1989;Ubezio et al, 1989). In other types of leukaemia it probably plays a more important role in clinical drug resistance (Mattern et al, 1989;Ma et al, 1987;Carulli et al, 1988;Sugawara et al, 1989 (Klumper et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…In two studies of adult ANLL in which MDR probably plays an important role, the effect of verapamil on uptake and cytotoxicity of anthracyclines was higher in cells from patients resistant to clinical chemotherapy (Maruyama et al, 1989;Tidefelt et al, 1988 tion of vinca-alkaloids and anthracyclines are not the only factors accounting for resistance to these classes of drugs (Ubezio et al, 1989;Rivera-Fillat et al, 1988). Diversion to some cellular compartment might play a role.…”

Section: Discussionmentioning

confidence: 99%

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Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia

Pieters

Hongo²,

Loonen³

et al. 1992

Br J Cancer

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Summary Although cellular drug resistance is considered to be an important cause of the poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the knowledge of drug resistance in these patients is very limited. Different aspects of drug resistance were studied in 17 children with relapsed ALL. The in vitro sensitivity profile was determined using the MTT assay. Cells from relapsed children were significantly more resistant to 6-thioguanine, prednisolone, cytosine arabinoside, daunorubicin (DNR) The use of combination chemotherapy in children with acute lymphoblastic leukaemia (ALL) presently results in a complete remission rate of more than 95%. With the best currently available treatment, about two thirds of these children will remain in continuous complete remission and can therefore be considered cured. Patients suffering from a relapse however have a cure rate which is much lower. One of the main causes of this poor prognosis is probably a resistance of the leukaemic cells to a number of drugs used for treatment (Rivera et al., 1989).At present the knowledge of drug resistance in childhood ALL is very limited. It is unknown how often, when, and for which drugs resistance is occurring. Currently, much attention is given to the multidrug resistance (MDR) phenomenon: a resistance to vinca-alkaloids and anthracyclines, mediated by the drug efflux pump P-glycoprotein (P-gp), that can at least be partially overcome by so-called resistance modifiers. The clinical significance of MDR in childhood ALL is still unknown. Recently, we and others adapted and improved assays to detect drug resistance of leukaemic cells obtained from patients (Weisenthal et al., 1986;Bird et al.,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia

Pieters

Hongo²,

Loonen³

et al. 1992

Br J Cancer

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“…Other studies, however, contradict the finding that P-gp expression is of clinical value. [29][30][31] Data on the prognostic significance of the other MDR proteins in childhood ALL are scarce. One study on a group of Indian ALL patients, most of whom were children, reported significantly higher MRP1 mRNA expression at relapse than at presentation or remission.…”

Section: Discussionmentioning

confidence: 99%

Multidrug resistance genes in infant acute lymphoblastic leukemia: Ara-C is not a substrate for the breast cancer resistance protein

et al. 2003

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“…Several observations, however, point to the involvement of the P-glycoprotein, as (i) the unresponsiveness of tumours derived from tissues with an intrinsically high P-glycoprotein expression (Fojo et al, 1987), (ii) the emergence of P-glycoprotein expression in specimens of relapsed state malignancies after chemotherapy (Ma et al, 1987;Goldstein et al, 1989;Volm et al, 1989;Musto et al, 1990;Pirker et al, 1991), and (iii) reports on the successful treatment of drug-resistant tumours by including the calcium channel blocker and P-glycoprotein binding drug verapamil in chemotherapy protocols (Dalton et al, 1989). However, other studies do not support the view of a frequently occurring link between elevated P-glycoprotein levels and therapy failures of leukaemias (Ito et al, 1989;Ubezio et al, 1989). Moreover, many clinically used antineoplastic drugs like ara C, cisplatin, or most alkylating agents do not even belong to the group of agents involved in the MDR-phenotype of cells selected in vitro.…”

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confidence: 99%

Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase π gene expression in primary and relapsed state adult and childhood leukaemias

Gekeler

Frese²,

Noller³

et al. 1992

Br J Cancer

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Summary In a variety of adult and childhood leukaemia cell samples collected at different states of the disease, we analysed in a series of sequentially performed slot-blot or Northern-blot hybridisation experiments the expression of genes possibly involved in multiple drug resistance (MDR) (mdrl/P-glycoprotein, DNA topoisomerase II, glutathione-S-transferase x), and the expression of the DNA topoisomerase I and histone 3.1 genes. Occasionally, P-glycoprotein gene expression was additionally examined by indirect immunocytofluorescence using the monoclonal antibody C219. No significant difference in mdrl/P-glycoprotein mRNA levels between primary and relapsed state acute lymphocytic leukaemias (ALL) was seen on average. Second or third relapses, however, showed a distinct tendency to an elevated expression of this multidrug transporter gene (up to 10-fold) in part well beyond the value seen in the moderately cross-resistant T-lymphoblastoid CCRF-CEM subline CCRF VCR 100. Increased mdrl/P-glycoprotein mRNA levels were also found in relapsed state acute myelogeneous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years. Topoisomerase I and topoisomerase II mRNA levels were found to be very variable. Whereas in all but one case of CLL topoisomerase II mRNA was not detected

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Failure to detect the P-glycoprotein multidrug resistant phenotype in cases of resistant childhood acute lymphocytic leukaemia

Cited by 26 publications

References 6 publications

Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia

Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia

Multidrug resistance genes in infant acute lymphoblastic leukemia: Ara-C is not a substrate for the breast cancer resistance protein

Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase π gene expression in primary and relapsed state adult and childhood leukaemias

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