Relevance of mdr1 gene expression in acute myeloid leukemia and comparison of different diagnostic methods.
In an attempt to determine the incidence and clinical relevance of mdr1 gene expression in acute myeloid leukemia (AML), we examined 126 specimens obtained from adult patients with de novo AML by slot blot and immunocytochemistry. We found a high incidence of mdr1 gene expression in newly diagnosed patients (27% by immunocytochemistry and 43% by slot blot). No difference was observed between newly diagnosed patients and relapsed patients. However, patients with resistant disease showed statistically higher incidence of mdr1 gene expression compared to the untreated and relapsing patients (60% versus 27% by immunocytochemistry, p 0.005; and 73% versus 45% by slot blot, p less than 0.05). The expression of mdr1 gene correlated significantly with clinical drug resistance: 62% of patients positive for mdr1-mRNA and 68% of patients positive for P-glycoprotein (P-gp) eventually developed resistance to chemotherapy, while this was the case for a lower percentage of patients who did not express mdr1 gene (only 23% by slot blot analysis, p = 0.0052, or 24% by immunocytochemistry, p = 0.0009). A combined parameter, mdr1-mRNA/P-gp, had a very high prognostic value in terms of specificity and sensitivity. All nine patients (100%) who were mdr1-mRNA+/P-gp+ progressed to clinical drug resistance afterward, whereas 11 of 13 (85%) patients who were mdr1-mRNA-1 P-gp- entered complete remission and only two patients later developed drug resistance (p = 0.0005). It could thus be used as a reliable parameter in clinical settings.
Service d'Hématologie, Hôtel-Dieu de Paris, Université Paris, France.
D C
DC
Zhou
J P
JP
Marie
A M
AM
Suberville
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Zittoun
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D012333:RNA, Messenger