Detection of a Multidrug Resistant Phenotype in Acute Non-Lymphoblastic Leukaemia

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

“…The molecular mechanisms of this clinically observed refractoriness of tumours to chemotherapy are still little understood. 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).…”

P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies

“…In contrast, we have previously shown significant levels of mdr-1 mRNA in a series of untreated primary breast cancers (Keith et al, 1990) Monoclonal antibodies have already been used to detect P-gp expression in several human tumours. C219, which reacts with an internal epitope of P-gp, has revealed P-gp expression in acute non-lymphoblastic leukaemia (Ma et al, 1987) as well as lung and ovarian carcinomas . Moreover, C219 has confirmed P-gp expression in both untreated and treated breast cancers (Salmon et al, 1989;Schneider et al, 1989).…”

P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy

“…Four tumours treated by chemotherapy showed a similar pattern of staining including a positive reaction (1+) within normal duct epithelium in two. Stromal staining (2+ ) was observed in a further tumour that had shown static disease ( Figure 1) (Gerlach et al, 1987), leukaemia (Ma et al, 1987) ovarian carcinoma (Bell et al, 1985) phaechromocytoma (Fojo et al, 1987) and evolving clinical resistance.…”