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

Daniela Damiani; Mario Tiribelli; Angela Michelutti; Antonella Geromin; Margherita Cavallin; Dora Fabbro; Annalisa Pianta; Michele Malagola; Giuseppe Damante; Domenico Russo; Renato Fanin

doi:10.1016/j.leukres.2010.01.008

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

Leuk Res. 2010 Jul;34(7):942-5. doi: 10.1016/j.leukres.2010.01.008. Epub 2010 Jan 31.

Authors

Daniela Damiani¹, Mario Tiribelli, Angela Michelutti, Antonella Geromin, Margherita Cavallin, Dora Fabbro, Annalisa Pianta, Michele Malagola, Giuseppe Damante, Domenico Russo, Renato Fanin

Affiliation

¹ Clinica Ematologica e Centro Trapianti e Terapie Cellulari C. Melzi, Azienda Ospedaliero-Universitaria di Udine, Dipartimento di Ricerche Mediche e Morfologiche, Università di Udine, Udine, Italy. daniela.damiani@uniud.it

PMID: 20122734
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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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