Myeloid Kanserlerde Kemik İliği Mikroçevresinin Metabolik Profilinin İncelenmesi

Abstract

ŞAHİN A. B., Investigation of the metabolic profile of the bone marrow microenvironment in myeloid cancers, Hacettepe University Graduate School of Health Sciences, Stem Cell Program Master Thesis, Ankara, 2024. Metabolic profiling of the leukemic niche is the best indicator of dynamic changes in leukemic cell metabolism at leukemia diagnosis, after treatment, and in relapsed/refractory disease. For this purpose, in this project, comparative metabolome analyses were performed between AML patients (N=28) and healthy donors (N=15) using bone marrow plasma samples, which are considered to best reflect the metabolic environment in the leukemic niche in vivo. Three main groups were formed for the analyses. In the first group, AML patient samples were compared with healthy donor samples to evaluate the changes caused by the leukemic cell mass in the metabolic profile of the bone marrow niche. In the second group, post-treatment and pre- treatment AML samples were compared in order to show the changes in the metabolic profile of the bone marrow niche after the clearance of the leukemic cell mass. In the third group, post-treatment AML and healthy donor samples were compared to evaluate the normalization of the bone marrow metabolic profile in recovered AML patients. The prominent metabolites/lipids in AML patient samples were triacylglycerol, sphingolipids/metabolites, phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphocholine), and fatty acids, which are associated with significantly increased lipid metabolism. Significant increases in phosphoglyceric acid, isomaltose, lactobionic acid, and citric acid levels were also found in relation to increased glycolysis. Also, in AML patients compared to healthy donors, the most affected metabolic pathways were found to be those related to galactose, glycerophospholipid, and ascorbate/aldarate metabolism.