title: Initial P-glycoprotein expression in childhood acute lymphoblastic leukemia: no evidence of prognostic impact in follow-up.
abstract: Treatment results in childhood acute lymphoblastic leukemia (ALL) have improved remarkably during the past 20 years, but still 25% of children cannot be permanently cured. Drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is the P-glycoprotein (P-gp)-mediated multiple-drug resistance (MDR). The authors prospectively analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a population-based series of 103 children with ALL treated according to intensive Nordic ALL protocols. Increased P-gp expression was detected in 55 patients (53%). With a cutoff value of 1% P-gp-positive blasts in bone marrow, no difference was found in event-free survival (EFS) or overall survival between children with low vs. increased P-gp expression. The 4-year EFS in the whole series was 77%. Patients with T-ALL had higher P-gp levels than the others, 3.6% vs. 1.0% (p = .002). P-gp expression did not correlate with the white blood cell count, age, sex, or cytogenetics. The authors conclude that the level of P-gp expression cannot be used as a tool for treatment stratification in childhood ALL.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, P.O.B. 281, FIN-00290 Helsinki, Finland. jukka.kanerva@helsinki.fi
authors.forename: J
authors.initials: J
authors.lastname: Kanerva
authors.forename: M I
authors.initials: MI
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 / Q000032:analysis*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1