Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells.
The expression of the MDR-1-encoded P-170 glycoprotein (P-170) associated with clinical multidrug resistance (MDR) was investigated in 52 consecutive patients with untreated acute myeloid leukemia (AML). P-170 expression was analyzed in correlation with CD34 expression and clinical response. Thirty of 52 patients expressed P-170 (58%). Eight of 30 P-170+ as compared with 16 of 22 P-170- patients achieved a complete remission (CR) (27% v 73%, P = .003). In 21 of 30 P-170+ patients, expression of the CD34 antigen was observed in greater than 10% of the blast cells, as compared with 14 of 22 P-170- patients (70% v 64%, P > .05). The CR rate of CD34+ and CD34- patients was 31% and 76%, respectively (P = .006). In AMLs that simultaneously expressed both P-170 and CD34, the CR rate was worse as compared with those negative for P-170 and CD34 (5% v 63%, P = .004). In 12 patients (8 P-170+, 4 P-170-) CD34 and P-170 expression were further characterized by double fluorescence studies. It was shown that P-170+ cells were largely, but not exclusively, restricted to the CD34+ cell population. For the 8 P-170+ AML samples, the median ratio of P-170+/P-170- in CD34+ cells was 4.845 (range, 0.60 to 25.00) as compared with 0.135 (range, 0.02 to 0.67) in CD34- cells. In these 12 AML samples, the presence of functional resistance as defined by reduced daunorubicin accumulation was evaluated in CD34+ and CD34- AML cells. In 8 of 8 P-170+ patients, intracellular daunorubicin accumulation in CD34+ AML blast cells was lower than in CD34- cells, and it increased after cyclosporin addition. No difference of intracellular daunorubicin accumulation was observed between CD34+ and CD34- AML cells of 4 P-170- patients. These data indicate that P-170 expression in AML with a heterogeneous CD34+ phenotype seems predominantly present in CD34+ AML blast cells.
te Boekhorst
P A
PA
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
de Leeuw
K
K
Schoester
M
M
Wittebol
S
S
Nooter
K
K
Hagemeijer
A
A
Löwenberg
B
B
Sonneveld
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002352:Carrier Proteins / Q000032:analysis*; D003630:Daunorubicin / Q000008:administration & dosage / Q000378:metabolism; D004351:Drug Resistance; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis*; D010641:Phenotype
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D018952:Antigens, CD34; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D003630:Daunorubicin