Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment.
The clinical significance of the multidrug resistance (MDR 1) gene phenotype was investigated in newly diagnosed AML and was compared with other clinical and biological prognostic factors in patients who received at least one course of induction therapy with intercalating agents and conventional doses of Ara-C. MDR 1 gene was overexpressed in 40% of the 110 cases of AML at presentation, MRP in 15% of the 48 patients tested for both markers. Both gene expressions were closely linked (p = 0.008). Except for a lower frequency in the "good risk" cytogenetic group, MDR 1 overexpression was not associated with other prognostic factors. In univariate analysis, MDR 1 overexpression, age over 50 years, and cytogenetic were associated with a higher rate of resistance to induction treatment. The overall survival was shorter in the case of intermediate or poor cytogenetics, high leukocytosis, MDR 1 overexpression, age over 50 years, secondary AML, and poor cytologic differentiation. Using multivariate analysis on 64 patients receiving intensive treatment, MDR 1 overexpression was the first significant prognostic factor for resistance to the first course of induction treatment. Cytogenetic analysis maintained its prognostic value only in MDR 1-negative patients. These data underline the value of MDR 1 gene expression as a powerful prognostic factor in AML for response to the first induction treatment and overall survival, sustaining the use of MDR 1 modulators for first-line therapy in this disease.
Hunault
M
M
Department of Hematology, Paris 6 University, Hôtel Dieu, France.
Zhou
D
D
Delmer
A
A
Ramond
S
S
Viguié
F
F
Cadiou
M
M
Perrot
J Y
JY
Levy
V
V
Rio
B
B
Cymbalista
F
F
Zittoun
R
R
Marie
J P
JP
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics; D010641:Phenotype; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins