الفهرس 
Chronic Myeloid Leukaemia (CML)Only 14 pages are availabe for public view
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Abstract
Background: chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by a reciprocal translocation between chromosomes 9 and 22 [t (9;22) (q34; q11)], creating the Philadelphia chromosome and bringing together the Breakpoint Cluster Region (BCR) and Abelson (ABL1) genes. The protein encoded by this fusion gene is a dysregulated tyrosine kinase that phosphorylates multiple downstream proteins resulting in changes in cell proliferation, DNA repair, differentiation and cell cycling.
Objecitves: The aim of our study was to assess PTCH1 gene expression and response of adult patients with chronic myeloid leukemia to imatinib.
Patients and Methods: A total of 55 individuals with chronic phase chronic myeloid leukemia between June 2015 and July 2017 enrolled in a retrospective study at the hematology clinic, Ain Shams University Hospital were studied. Each patient gave informed consent for the withdrawal and use of biological samples. Following diagnosis of Ph-positive CP-CML, patients were started on imatinib,400 mg daily. All patients participating in the study.
Results: PTCH1 gene mutation was found in 80 % of patients diagnosed with CML however it was only found in 20 % of normal population. (P-value= <0.001). Patients with imatinib response had a median of PTCH1 expression of 2.49, compared to 2.41 in the imatinibfailure group(P = 0.5). Histogram of relation between imatinib response and PTCH 1 expression. Cumulative incidence of imatinib failure after 6 months of treatment in males is 33 % while in females 8 %. However (HR= 2.6, P= 0.1). Cumulative incidence of imatinib failure after 6 months of treatment in patients with high PTCH1 expression is 27.8 % while in those with low expression is 44.4 %. However (HR= 0.6, P= 0.5). That may indicate that the level of PTCH1 expression may not affect the response to imatinib. Progression free survival in group with high PTCH 1 expression was 72.2 % while in the low expression group 55.6 %. P value= 0.9.
Conclusion: The study demonstrates that level of PTCH 1 did not affect imatinib response. Therefore, PTCH1 is not a valid biomarker for imatinib resistancein cml patients.