title: Multiple drug resistance mediated by P-glycoprotein is not a major factor in a slow response to therapy in childhood ALL.
abstract: 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.
authors.affiliation: Children's Hospital, University of Helsinki, Finland. jukka.kanerva@helsinki.fi
authors.forename: J
authors.initials: J
authors.lastname: Kanerva
authors.forename: M
authors.initials: M
authors.lastname: Tiirikainen
authors.forename: A
authors.initials: A
authors.lastname: Mäkipernaa
authors.forename: P
authors.initials: P
authors.lastname: Riikonen
authors.forename: M
authors.initials: M
authors.lastname: Möttönen
authors.forename: T T
authors.initials: TT
authors.lastname: Salmi
authors.forename: T
authors.initials: T
authors.lastname: Krusius
authors.forename: U M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001752:Blast Crisis; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage
chemical_list: 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