الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm resulting from the malignant transformation of a primitive hematopoietic stem cell. It results from reciprocal translocation between chromosome 9 and 22 t(9;22) (q34;q11) generating BCR-ABL, a tyrosine kinase encoding oncogene. This gives rise to the uncontrolled proliferation primarily of the granulocytic and megakaryocytic lineages, resulting in the accumulation of immature granulocytic precursors in the bone marrow, blood, and other organs and transforming the HSC into the CML stem cell, which then gives rise to a clonal myeloproliferative neoplasm.
Abnormal interactions between the BCR-ABL oncoprotein and other cytoplasmic molecules lead to the disruption of key cellular processes.
The feasibility of discontinuation of TKI therapy (with close monitoring) in carefully selected patients who have achieved and maintained deep molecular response (≥MR 4.0; ≤0.01 % BCR-ABL1 IS) for ≥ 2 or more years has been evaluated in several clinical studies.
Monitoring of minimal residual disease with quantitative reverse transcription PCR (RQ-PCR), enables definition of the depth of molecular response (MR), has prognostic relevance and may identify early resistance due to mutations that guide changes in TKI usage.
Proteomics is the study of the set of proteins encoded by the genome, including its isoforms, modifications, interactions, and structure.
Mass spectrometry (MS) is the technique of choice for protein identification and had a pivotal role in our understanding of cellular function. MALDI-TOF mass spectrometry can detect peptides with low molecular weights, which makes it a useful technique for plasma peptide profiling. Magnetic beads have been used and considered as a promising material for convenient and efficient enrichment of peptides and proteins in biological samples. The combination of MALDI-TOF MS and magnetic beads enables the high throughput and sensitive investigation of peptides and proteins.
In the present study; we aimed at assessment of serum proteome pattern in CML patients at initial diagnosis and six months after TKIs therapy to detect potential biomarker profile in correlation with MRD as detected by Quantitative RT-PCR and with healthy subjects. Thus, trying to find out if they have any prognostic value in CML. In our study, we used Hydrophobic Interaction chromatography (HIC-8 MBs), Ultraflextreme MALDI-TOF MS and ClinProTM3.0 to differentiate between protein profile of pre- and post- treated after six months of TKIs CML patients and healthy control subjects and to validate plasma peptide profiling in a group of Egyptian patients with chronic phase CML.
Our study included 30 adult CML patients attending the Hematology Outpatient Clinic, Alexandria Main University Hospital and Medical Research Institute, and 30 healthy controls matched for age and sex. All patients had newly diagnosed CML.