Expression of resistance genes in acute leukemia.
To evaluate the frequency and the prognostic value of different mechanisms of drug resistance in acute leukemias, we investigated the expression of mdr1 by immunocytochemistry, mRNA slot blot or RT-PCR in 182 cases of adult acute myeloid and 37 cases of adult lymphoblastic leukemia. Before treatment, 39% of de novo AML, 38% of secondary AML, and 7% of de novo ALL exhibited a high level of mdr1 mRNA. After chemotherapy, the frequency of mdr1 gene expression in ALL raised dramatically to 60% (P < 0.005), while no significant change was found for AML cases. In 91 patients treated with MDR-related drugs, mdr1 gene expression was related to the failure of chemotherapy (P < 0.0001). The overexpression of multidrug resistance-associated protein (mrp) and anionic glutathione S-transferase (GST pi) was also investigated in 38 and 61 AML patients respectively. An overexpression of mrp gene was noted in 39% of the cases. For GST pi gene, the frequency of overexpression was 28%. A positive and significative correlation was found among mdr1, mrp and GST pi genes expression.
Zhou
D C
DC
Laboratoire de Cinétique et de Cultures Cellulaires, Formation de Recherche Associée Claude Bernard sur le Traitement des Hémopathies Malignes, Paris, France.
Hoang-Ngoc
L
L
Delmer
A
A
Faussat
A M
AM
Russo
D
D
Zittoun
R
R
Marie
J P
JP
D014408:Biomarkers, Tumor; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics
D014408:Biomarkers, Tumor; D005982:Glutathione Transferase