Fludarabine-based induction therapy does not overcome the negative effect of ABCG2 (BCRP) over-expression in adult acute myeloid leukemia patients.
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.
Damiani
Daniela
D
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
Tiribelli
Mario
M
Michelutti
Angela
A
Geromin
Antonella
A
Cavallin
Margherita
M
Fabbro
Dora
D
Pianta
Annalisa
A
Malagola
Michele
M
Damante
Giuseppe
G
Russo
Domenico
D
Fanin
Renato
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012074:Remission Induction; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D014740:Vidarabine; C116614:ABCG2 protein, human; C024352:fludarabine; C421109:multidrug resistance-associated protein 1