[Detection of the resistance to Ara-C blast cells in acute myeloid leukemia using flow cytometry].
Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. A resistance index (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with Ara-C to that incorporated in the absence of Ara-C. In Ara-C sensitive and resistant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone marrow samples from patients with de novo AML treated by a regimen containing Ara-C. A first group of nine patients with high RI values included only drug resistant (DR) patients; a second group of 63 patients with low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values included 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.
Lacombe
F
F
Laboratoire d'hématologie, hôpital Haut-Lévêque, Pessac, France.
Belloc
F
F
Dumain
P
P
Puntous
M
M
Cony-Makhoul
P
P
Bernard
P
P
Boisseau
M R
MR
Reiffers
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000187:drug effects; D002999:Clone Cells; D003561:Cytarabine / Q000494:pharmacology / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016196:S Phase; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D003561:Cytarabine
Détection de la résistance à l'Ara-C des cellules blastiques de leucémie aiguë myéloïde par cytométrie en flux.