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Identifier

000397371

Title

Μελέτη νέων αναλόγων του Gleevec στη λευχαιμική σειρά K562

Alternative Title

A study of newly synthesised compounds based on Gleevec in K562 leukemic cell line

Author

Μάρκου, Παναγιώτα Η.

Thesis advisor

Τσιώτης, Γεώργιος

Reviewer

Γανωτάκης, Δημήτριος Φ.
Περγαντής, Σπύρος Α.

Abstract

Chronic Myelogenous Leukemia is a type of cancer which affects the hemopoiesis procedure. This malignancy is a result of a reciprocal translocation between chromosomes 9 and 22. The fusion of parts from these two chromosomes is a new chromosome called the Philadelphia Chromosome (Ph). This new chromosome encodes the p210^BCR-ABL protein. This protein has a kinase domain, which is constitutively active, giving downstream signals for uncontrolled proliferation and cell growth. The research for the development of inhibitors for the kinase domain on p210^BCR-ABL was essential. Gleevec, is the first drug that was released and was quite effective for inhibiting the activity of this protein. However, it is not a permanent cure since the leukemic cells have developed resistance mechanisms for this drug, making it no longer effective. This is causing the disease to progress rapidly to the final stage. New drugs are always a goal, resulting in the synthesis of new compounds. Those novel compounds were tested in vitro, on K562 cell line by the method of MTT and the IC₅₀ values were calculated. Also, the compounds were tested for toxicity effects on white blood cells and red blood cells and for the induction of early apoptosis in K562 cells. In addition, proteome analysis of K562 cells, pre-incubated with the two novel compounds which had the lowest IC₅₀ values and Gleevec, was conducted by Electrospray Tandem Mass Spectrometry coupled with Liquid Chromatography (nLC-ESI-MS / MS). In total, 2959 proteins were identified from which 684 were statistically significant and were found to be differentiated.

Language

Greek

Subject

Chronic Myelogenous Leukemia

Electrospray Tandem Mass Spectrometry Coupled with nano-Liquid Chromatography (nLC-ESI-MS/MS)

IC50

New Compounds

Philadelphia Chromosome (Ph)

Protein p210BCR-ABL

Proteomics

Tyrosine Kinase Inhibitors (TKIs)

Αναστολείς των Κινασών της Τυροσίνης (TKIs)