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 ad...
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| Published in | Leukemia research Vol. 34; no. 7; pp. 942 - 945 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Elsevier Ltd
01.07.2010
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| Abstract | 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. |
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| AbstractList | 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. 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. |
| Author | Tiribelli, Mario Cavallin, Margherita Russo, Domenico Damiani, Daniela Pianta, Annalisa Fanin, Renato Damante, Giuseppe Geromin, Antonella Fabbro, Dora Malagola, Michele Michelutti, Angela |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20122734$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1111/j.1365-2141.2006.06390.x 10.1242/jcs.113.11.2011 10.1158/1078-0432.CCR-04-1895 10.1182/blood.V98.13.3575 10.1046/j.1365-2141.1999.01172.x 10.1158/1078-0432.CCR-04-0795 10.1182/blood.V92.7.2322 10.1111/j.1365-2141.2005.05745.x 10.1038/sj.leu.2404692 10.1080/01621459.1958.10501452 10.1182/blood-2002-01-0271 10.1073/pnas.95.26.15665 10.1038/sj.leu.2402723 10.1002/cyto.990090404 10.1007/s00277-007-0269-7 |
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| Snippet | Abstract Over-expression of multidrug resistance (MDR) proteins PGP and BCRP has a negative prognostic impact in acute myeloid leukemia (AML) patients.... Over-expression of multidrug resistance (MDR) proteins PGP and BCRP has a negative prognostic impact in acute myeloid leukemia (AML) patients. Inclusion of... |
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| SubjectTerms | 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 |
| Title | Fludarabine-based induction therapy does not overcome the negative effect of ABCG2 (BCRP) over-expression in adult acute myeloid leukemia patients |
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