CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia AML of older ageReport as inadecuate




CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia AML of older age - Download this document for free, or read online. Document in PDF available to download.

Annals of Hematology

, Volume 86, Issue 5, pp 329–337

First Online: 06 March 2007Received: 04 December 2006Accepted: 26 January 2007

Abstract

Clinical resistance to chemotherapy in acute myeloid leukemia AML is associated with the expression of the multidrug resistance MDR proteins P-glycoprotein, encoded by the MDR1-ABCB1 gene, multidrug resistant-related protein MRP-ABCC1, the lung resistance-related protein LRP, or major vault protein MVP, and the breast cancer resistance protein BCRP-ABCG2. The clinical value of MDR1, MRP1, LRP-MVP, and BCRP messenger RNA mRNA expression was prospectively studied in 154 newly diagnosed AML patients ≥60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001. Higher BCRP mRNA was associated with secondary AML p < 0.05. MDR1 and BCRP mRNA were highly significantly associated p < 0.001, as were MRP1 and LRP mRNA p < 0.001 expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1-BCRP coexpression, were associated with a lower complete response CR rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1-BCRP coexpression remained significantly associated with a lower CR rate p = 0.03, thereby identifying a clinically resistant subgroup of elderly AML patients.

KeywordsMDR1 MRP1 LRP BCRP Genes Elderly AML  Download fulltext PDF



Author: Marry M. van den Heuvel-Eibrink - Bronno van der Holt - Alan K. Burnett - Wolfgang U. Knauf - Martin F. Fey - Gregor E

Source: https://link.springer.com/



DOWNLOAD PDF




Related documents