INTRODUCTION: Drug resistance and relapse are considered to be the major reasons for treatment failure in acute myeloid leukemia (AML). There is limited data on the role of ABC transporter expression on in vitro sensitivity to cytarabine (Ara-C) and daunorubicin (Dnr) in primary AML cells. PATIENTS & METHODS: RNA expression levels of 12 ABC transporters were analyzed by real-time quantitative PCR in 233 de novo adult acute myeloid leukemia patients. Based on cytarabine or Dnr IC50, the samples were categorized as sensitive, intermediate and resistant. Role of candidate ABC transporter RNA expression on in vitro cytotoxicity, treatment outcome post therapy as well as the influence of various prognostic markers on ABC transporter expression were analyzed. RESULTS: Expression of ABCC3 and ABCB6 were significantly higher in Dnr-resistant samples when compared with Dnr-sensitive samples. Increased ABCC1 expression was associated with poor disease-free survival in this cohort of patients. CONCLUSION: This comprehensive analysis suggests ABCC1, ABCC3, ABCB6 and ABCA5 as probable targets which can be modulated for improving chemotherapeutic responses.
INTRODUCTION: Drug resistance and relapse are considered to be the major reasons for treatment failure in acute myeloid leukemia (AML). There is limited data on the role of ABC transporter expression on in vitro sensitivity to cytarabine (Ara-C) and daunorubicin (Dnr) in primary AML cells. PATIENTS & METHODS: RNA expression levels of 12 ABC transporters were analyzed by real-time quantitative PCR in 233 de novo adult acute myeloid leukemiapatients. Based on cytarabine or Dnr IC50, the samples were categorized as sensitive, intermediate and resistant. Role of candidate ABC transporter RNA expression on in vitro cytotoxicity, treatment outcome post therapy as well as the influence of various prognostic markers on ABC transporter expression were analyzed. RESULTS: Expression of ABCC3 and ABCB6 were significantly higher in Dnr-resistant samples when compared with Dnr-sensitive samples. Increased ABCC1 expression was associated with poor disease-free survival in this cohort of patients. CONCLUSION: This comprehensive analysis suggests ABCC1, ABCC3, ABCB6 and ABCA5 as probable targets which can be modulated for improving chemotherapeutic responses.
Entities:
Keywords:
ABC transporters; acute myeloid leukemia; drug resistance; in vitro cytotoxicity
Authors: Maria Kolesnikova; Aleksandra Sen'kova; Sofia Tairova; Viktor Ovchinnikov; Tatiana Pospelova; Marina Zenkova Journal: J Pers Med Date: 2019-05-07
Authors: Cora S Thiel; Andreas Huge; Swantje Hauschild; Svantje Tauber; Beatrice A Lauber; Jennifer Polzer; Katrin Paulsen; Hartwin Lier; Frank Engelmann; Burkhard Schmitz; Andreas Schütte; Liliana E Layer; Oliver Ullrich Journal: NPJ Microgravity Date: 2017-08-31 Impact factor: 4.415
Authors: Zsófia Rakvács; Nóra Kucsma; Melinda Gera; Barbara Igriczi; Katalin Kiss; János Barna; Dániel Kovács; Tibor Vellai; László Bencs; Johannes M Reisecker; Norbert Szoboszlai; Gergely Szakács Journal: Cell Mol Life Sci Date: 2019-05-03 Impact factor: 9.261