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.
Del Principe, M., Del Poeta, G., Maurillo, L., Buccisano, F., Venditti, A., Tamburini, A., et al. (2003). P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia. BRITISH JOURNAL OF HAEMATOLOGY, 121(5), 730-738.
|Tipologia:||Articolo su rivista|
|Citazione:||Del Principe, M., Del Poeta, G., Maurillo, L., Buccisano, F., Venditti, A., Tamburini, A., et al. (2003). P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia. BRITISH JOURNAL OF HAEMATOLOGY, 121(5), 730-738.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||giu-2003|
|Titolo:||P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia|
|Autori:||Del Principe, M; Del Poeta, G; Maurillo, L; Buccisano, F; Venditti, A; Tamburini, A; Bruno, A; Cox, M; Suppo, G; Tendas, A; Giannì, L; Postorino, M; Masi, M; Del Principe, D; Amadori, S|
|Appare nelle tipologie:||01 - Articolo su rivista|