Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry.
To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.
Guerci
A
A
Service de Médecine A. CHU Brabois, Vandoeuvre-lès-Nancy, France.
Merlin
J L
JL
Missoum
N
N
Feldmann
L
L
Marchal
S
S
Witz
F
F
Rose
C
C
Guerci
O
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001752:Blast Crisis / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D001772:Blood Cell Count; D001853:Bone Marrow / Q000737:chemistry* / Q000473:pathology; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000648:ultrastructure; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D011379:Prognosis; D011446:Prospective Studies; D011803:Quinine / Q000008:administration & dosage; D012074:Remission Induction; D012306:Risk; D016879:Salvage Therapy; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D018952:Antigens, CD34; D009363:Neoplasm Proteins; D003561:Cytarabine; D011803:Quinine; D008942:Mitoxantrone; C002205:zorubicin; D015255:Idarubicin; D003630:Daunorubicin