Date

2019

Author

Pekşen, Ceren

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Hematologic cancers have two origins: myeloid and lymphoid. While lymphatic leukemia, originate from the lymphoid cell line, acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) originate from the myeloid cell line. CML is granulocyte cancer and in this disease, as well as granulocytes, the number of cells that cause blood clotting, which are called platelets, may increase in the blood. In CML, a non-hereditary genetic abnormality, Philadelphia chromosome, where a structural change occurs in chromosome 22, is seen in blood cells. Acute lymphoblastic leukemia (ALL), on the other hand, is caused by abnormally uncontrolled and excessive proliferation of lymphoblasts. ALL is responsible for 80% of childhood leukemia and is common between 3-7 years of age. It can also be seen in adults and accounts for 20% of all adult leukemia. Interestingly, it was recorded that CML in its blast phase can turn into acute leukemia. It is not known which mutations cause this conversion. Since all leukemia subtypes stem from the bone marrow, the gold standard for the diagnosis of leukemia types is genetic testing via invasive bone marrow biopsy, but it has a healing process and can have psychological impacts, especially on children, thus recently, metabolomics, non-invasive and fast methods that can help in early diagnosis are being studied in leukemia. The cells obtained via bone marrow biopsy are examined for chromosomal abnormalities with cytogenetics analysis. In this study, the metabolic differences of Jurkat (ALL) and K562 (CML-BP) cell lines were aimed to be evaluated using HPLC-MS. Quantitative and quasi-quantitative studies were held to have an idea on the amounts of metabolites in each cell line. After measuring the concentrations of lactic acid and citric acid with the use of their authentic standards, a mass screening was performed on both cell lines, and it was seen that the metabolisms that are mainly affected during the conversion are tyrosine, arginine and proline, and glutathione metabolisms. Thus, existence of indicator metabolites of these related pathways were scanned. Intensities of the confirmed metabolites were compared. This study is the first metabolomics study that focuses on the blastic transformation of CML to ALL. Results of this study can be used in further studies to define a differentiating pattern for CML and ALL.

Subject Keywords

Myeloid leukemia., Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Metabolomics, LC-MS, Oncometabolites.

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http://etd.lib.metu.edu.tr/upload/12624440/index.pdf
https://hdl.handle.net/11511/44364

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Graduate School of Natural and Applied Sciences, Thesis