title: P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia.
abstract: Concurrent resistance mechanisms, such as P-glycoprotein (PGP) and bcl-2, may contribute to a worse outcome in adult acute lymphoblastic leukaemia (ALL). Between 1990 and 2000, we analysed PGP and bcl-2 by flow cytometry, using two anti-PGP (C219 and JSB-1) monoclonal antibodies (mAbs) and an anti-bcl-2 mAb in 115 de novo adult ALL patients. Both a longer overall survival (OS) and longer disease-free survival (DFS) were observed in PGP-negative patients (23%vs 0% at 3 years, P = 0.011 and 29%vs 0% at 2 years, P = 0.006 for C219 respectively; 42%vs 0% at 1.5 years, P = 0.004 and 53%vs 0% at 8.5 months, P = 0.00006 for JSB-1 respectively). Bcl-2 positivity was associated with a significantly higher complete remission rate (90%vs 66%, P = 0.01). Moreover, in 69 patients not presenting with either t(9;22) or B-mature immunophenotype, PGP negativity (JSB-1) maintained its significant favourable prognostic impact with regard to OS (41%vs 0% at 1.5 years, P = 0.009) and DFS (83%vs 0% at 6 months, P = 0.0005). Importantly, within a subset of 62 patients with normal (n = 31) or unknown (n = 31) karyotype, PGP (JSB-1)-negative patients showed both a significantly longer OS and DFS (63%vs 0% at 1.4 years, P = 0.018 and 84%vs 0% at 6 months, P = 0.001 respectively). In multivariate analysis, JSB-1 (P = 0.008) and cytogenetics (P = 0.02) were found to be independent prognostic factors with regard to DFS. Therefore, in adult ALL, PGP and bcl-2 represent sensitive indicators of clinical outcome, and potential targets of novel molecules aimed at overcoming chemoresistance and recurrent relapses.
authors.affiliation: Department of Haematology, University Tor Vergata, St Eugenio Hospital, Roma, Italy. midelprincipe@tiscalinet.it
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Del Principe
authors.forename: Giovanni
authors.initials: G
authors.lastname: Del Poeta
authors.forename: Luca
authors.initials: L
authors.lastname: Maurillo
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Anna
authors.initials: A
authors.lastname: Tamburini
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Cox
authors.forename: Giovanna
authors.initials: G
authors.lastname: Suppo
authors.forename: Andrea
authors.initials: A
authors.lastname: Tendas
authors.forename: Laura
authors.initials: L
authors.lastname: Giannì
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Postorino
authors.forename: Mario
authors.initials: M
authors.lastname: Masi
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Principe
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2