Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide.

Autor: Turk S; Department of Biochemistry, Hacettepe University, Ankara, Turkey., Turk C; Department of Medical Microbiology, Lokman Hekim University, Ankara, Turkey., Akbar MW; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey., Kucukkaraduman B; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey., Isbilen M; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey., Demirkol Canli S; Molecular Pathology Application and Research Center, Hacettepe University, Ankara, Turkey., Malkan UY; Department of Hematology, University of Health Sciences, Ankara, Turkey., Okay M; Department of Hematology, Hacettepe University, Ankara, Turkey., Ucar G; Department of Biochemistry, Hacettepe University, Ankara, Turkey., Sayinalp N; Department of Hematology, Hacettepe University, Ankara, Turkey., Haznedaroglu IC; Department of Hematology, Hacettepe University, Ankara, Turkey., Gure AO; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Nov 25; Vol. 15 (11), pp. e0242497. Date of Electronic Publication: 2020 Nov 25 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0242497
Abstrakt: Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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