Fludarabine-based induction therapy does not overcome the negative effect of ABCG2 (BCRP) over-expression in adult acute myeloid leukemia patients

• Published in: Leukemia research Vol. 34; no. 7; pp. 942 - 945
• Main Authors: Damiani, Daniela, Tiribelli, Mario, Michelutti, Angela, Geromin, Antonella, Cavallin, Margherita, Fabbro, Dora, Pianta, Annalisa, Malagola, Michele, Damante, Giuseppe, Russo, Domenico, Fanin, Renato
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2010
• Subjects: Acute Disease; Acute myeloid leukemia; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - physiology; ATP-Binding Cassette, Sub-Family B, Member 1 - physiology; BCRP; Disease-Free Survival; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Female; Fludarabine; Gene Expression Regulation, Leukemic; Hematology, Oncology and Palliative Medicine; Humans; Induction therapy; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - metabolism; Male; Middle Aged; Multidrug Resistance-Associated Proteins - physiology; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Prognosis; Remission Induction; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Vidarabine - pharmacology; Young Adult; BCRP; Fludarabine; Prognosis; Acute myeloid leukemia; Induction therapy
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2010.01.008

Abstract Over-expression of multidrug resistance (MDR) proteins PGP and BCRP has a negative prognostic impact in acute myeloid leukemia (AML) patients. Inclusion of fludarabine in induction chemotherapy increases remission rate in PGP over-expressing cases. We investigated the role of BCRP in 138 adult AML patients receiving induction therapy with fludarabine. None of the MDR-related proteins influenced complete remission attainment. Conversely, high levels of BCRP significantly affected disease-free survival, as higher relapse rates (48.5% vs 28.5%) and earlier relapse occurred in BCRP+ patients. Also overall survival was affected by BCRP positivity, and survival significantly worsened in case of concomitant PGP and BCRP over-expression.