CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age

van den Heuvel-Eibrink, Marry M; van der Holt, Bronno; Burnett, Alan K; Knauf, Wolfgang U; Fey, Martin F; Verhoef, Gregor E G; Vellenga, Edo; Ossenkoppele, Gert J; Löwenberg, Bob; Sonneveld, Pieter (2007). CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age. Annals of hematology, 86(5), pp. 329-37. Berlin: Springer 10.1007/s00277-007-0269-7

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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 >or=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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Fey, Martin

ISSN:

0939-5555

ISBN:

17340137

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:53

Last Modified:

09 Mar 2022 15:23

Publisher DOI:

10.1007/s00277-007-0269-7

PubMed ID:

17340137

Web of Science ID:

000245894900002

BORIS DOI:

10.48350/22400

URI:

https://boris.unibe.ch/id/eprint/22400 (FactScience: 34528)

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