Daunorubicin (DNR) accumulation in fresh leukemic cells: correlation with clinical and biological features.
The DNR accumulation (DNR Acc) and the verapamil (VRP) index (percent increase of VRP on DNR accumulation) was studied by using flow cytometry. Fresh leukemic mononuclear bone marrow blasts from 80 unselected ANLL patients' samples were incubated with DNR in the presence or absence of VRP. The DNR accumulation was determined by flow cytometry. The median DNR Acc was 28 (range: 4-101) and the median VRP index was 4% (range 0-53). VRP significantly enhanced DNR Acc in 42 of the ANLL samples (52.5%). DNR Acc or VRP index were not influenced by age, sex, or WBC counts. Only the FAB subclassification and the blast immunophenotyping were found to influence the parameters studied here. The lowest DNR Acc was found in M0 and M6 blast cells (15 range 0-46 and 10.5 range 8-13 respectively). M4 and M5 ANLL samples accumulated significantly more DNR than M0 and M6 blast cells. The VRP index was significantly higher in M0 compared with M1 and M2 samples, as well as in M4 compared with M1 samples. A slightly positive correlation was found between the percentage of CD34-positive cells in the CD34-positive samples and DNR Acc. In this study, DNR Acc and the VRP index were not significantly correlated with the response to chemotherapy or survival. In conclusion, this study shows that ANLL leukemic cells differ in anthracyclin accumulation and response to VRP in vitro.
Boiron
J M
JM
Service des maladies du sang, Hopital Haut-Lévêque, Pessac, France.
Belloc
F
F
Montastruc
M
M
Cony-Makhoul
P
P
Marit
G
G
Puntous
M
M
Dumain
P
P
Lacombe
F
F
Dubosc-Marchenay
N
N
Fabères
C
C
D000208:Acute Disease; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D017211:Treatment Failure; D014700:Verapamil / Q000494:pharmacology*
D003561:Cytarabine; D014700:Verapamil; D015255:Idarubicin; D003630:Daunorubicin