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

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.

• Authors: Daniela Damiani, Mario Tiribelli, Angela Michelutti, Antonella Geromin, Margherita Cavallin, Dora Fabbro, Annalisa Pianta, Michele Malagola, Giuseppe Damante, Domenico Russo, Renato Fanin
• Journal: Leukemia research (Leuk Res) Vol. 34 Issue 7 Pg. 942-5 (Jul 2010) ISSN: 1873-5835 [Electronic] England
• PMID: 20122734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Multidrug Resistance-Associated Proteins
• Neoplasm Proteins
• Vidarabine
• fludarabine
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (physiology)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (biosynthesis, genetics, physiology)
• Acute Disease
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Disease-Free Survival
• Drug Resistance, Neoplasm (drug effects, genetics)
• Female
• Gene Expression Regulation, Leukemic
• Humans
• Leukemia, Myeloid (drug therapy, metabolism)
• Male
• Middle Aged
• Multidrug Resistance-Associated Proteins (physiology)
• Neoplasm Proteins (biosynthesis, genetics, physiology)
• Remission Induction
• Vidarabine (administration & dosage, analogs & derivatives, pharmacology)
• Young Adult