In vitro drug sensitivity of leukemic progenitors and P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome.
We have investigated the self-renewal capacity (PE2) and in vitro sensitivity to cytosine-arabinoside (ara-C) and daunorubicine (DNR) of leukemic progenitors (CFU-AML) to determine the significance of these tests for predicting induction treatment outcome in 75 adult acute myeloid leukemia (AML) patients. In addition, in a part of this group of patients (n = 46) we determined the expression of P-glycoprotein (P-gp) immunocytochemically and correlated those results with the therapeutic response. We have evaluated 66 patients who showed the following responses: 28/66 complete remissions (CR), 16/66 resistant leukemias (RL) and 22/66 early deaths (ED). The PE2 value was significantly higher in patients with RL than in patients with CR (p < 0.00375). CFU-AML sensitivity to ara-C and DNR alone was not different between response groups, but the difference in CFU-AML sensitivity to the combination of drugs between patients with CR and RL was not significant, although a trend was noted (p < 0.06). P-gp expression was found in only 1/18 patients who achieved CR but in 9/11 patients with RL and 7/11 patients with ED, which is a highly significant difference (p < 0.0006). We concluded that both PE2 and P-gp expression in AML cells are valuable predictors of therapeutic response in adult AML and should be included in creating the best therapeutic approach to AML patients.
Basara
N
N
Institute of Hematology, Clinical Center of Serbia, Belgrade, Yugoslavia.
Radosević-Radojković
N
N
Colović
M
M
Bosković
D
D
Rolović
Z
Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology / Q000627:therapeutic use*; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D012074:Remission Induction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003561:Cytarabine; D003630:Daunorubicin