ATRA - differentiation leukemia therapy

Sasi, Biljana (2012) ATRA - differentiation leukemia therapy. Bachelor's thesis, Faculty of Science > Department of Biology.

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The bulk of this work is the description of myelopoiesis, differentiation pathway from the myeloid precursor to the final lineage of granulocytes (neutrophils, eosinophils, basophils) and agranulocytes (monocytes/macrophages). Disruption of differentiation mechanisms, as inhibition of lineage-specific differentiation factors and biosignalisation pathways Ras/Raf/MEK/ERK and PI3K/Akt/mTOR/S6K leads to excessive formation of immature cells, where they accumulate in the bone marrow and the bloodstream, so it all results with leukemia. Otherwise, APL is described as a disease with a fatal outcome within only a few weeks after diagnosis and is characterized by a balanced reciprocal translocation between chromosomes 15 and 17. The result is a fusion between PML gene and retinoic acid receptor α (RARα) which causes a conformational change whereby co-repressor HDAC remains bound to this newly synthesized hybrid protein PML/RARα at physiological concentrations of RA. The final consequence is an increased proliferation of abnormal promyelocytes. All that leads to disruption of normal differentiation toward granulocytes. However, a clinical application of ATRA and ATO in APL treatment achieved a considerable success. Importanly, ATRA and ATO properties such as enhanced modification or degradation of PML/RARα oncoprotein, mediated by intracellular caspases and a cytoplasmic complex proteasome, might provide a plausible explanation for the appreciable efficacy of this combination therapy in APL patients.

Item Type: Thesis (Bachelor's thesis)
Supervisor: Marijanović, Inga
Date: 2012
Number of Pages: 22
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 16 Oct 2014 12:30
Last Modified: 16 Oct 2014 12:30

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