Multiple drug resistance mediated by P-glycoprotein is not a major factor in a slow response to therapy in childhood ALL.
In childhood acute lymphoblastic leukemia (ALL), early response to treatment is an important prognostic factor and drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR). We analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a series of 118 children with ALL, 103 at diagnosis and 15 at relapse. Increased P-gp expression was found in 55 (53%) patients at diagnosis and in 11 (73%) at relapse. We also analyzed the bone marrow aspirate slides for early response to treatment in a central review. No correlation was found between P-gp and early response. Patients with T-ALL had higher P-gp levels than the others, 5.3% versus 1.0% (P = .002). We conclude that P-gp-mediated multiple drug resistance is not a factor in a slow response to ALL induction therapy.
Kanerva
J
J
Children's Hospital, University of Helsinki, Finland. jukka.kanerva@helsinki.fi
Tiirikainen
M
M
Mäkipernaa
A
A
Riikonen
P
P
Möttönen
M
M
Salmi
T T
TT
Krusius
T
T
Saarinen-Pihkala
U M
UM
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate