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العنوان
Cortactin expression in chronic myeloid leukemia \
المؤلف
Shaheen, Mohammed Abdel-Moaty Ebraheem.
هيئة الاعداد
باحث / محمد عبدالمعطي إبراهيم شاهين
مشرف / تامر محمد أحمد إبراهيم
مشرف / دينا سمير محمد عيسى
مشرف / هايدي سيد محمد
تاريخ النشر
2022.
عدد الصفحات
148 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
أمراض الدم
تاريخ الإجازة
1/1/2022
مكان الإجازة
جامعة عين شمس - كلية الطب - أمراض الدم الاكلينيكية
الفهرس
Only 14 pages are availabe for public view

from 148

from 148

Abstract

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disease characterized by leukocytosis and an accumulation of granulocytes and their precursors. The Philadelphia chromosome t(9;22)(q34;q11.2) and the constitutive expression of the fusion protein Break-point Cluster Region and Abelson (BCR–ABL1) are the unique hallmarks of CML cells (Vetrie et al., 2020).
CML progresses through three distinct phases: A chronic phase that is easily controlled, followed by an ill-defined unstable accelerated phase, leading to a terminal blastic phase. The blastic phase resembles acute leukemia and is highly refractory to chemotherapy with ≤20% response rate (Ali et al., 2020).
The therapeutic approach to CML has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. Patients in the chronic phase can be treated with tyrosine kinases inhibitors (TKIs). Unfortunately, accelerated and blast phases are not responsive to TKIs likely because their progression is not affected by BCR-ABL (Carofiglio et al., 2020).
High cortactin expression in many hematological malignancies was reported by many authors to be correlated with other adverse prognostic factors. Aref et al. 2020 reported that high expression of cortactin at diagnosis was a bad prognostic marker of T-ALL patients’ outcome. Moreover, cortactin expression could be used as a biomarker for refining risk stratification of T-ALL. Similar results were reported by Velázquez-Avila et al. 2019 in B-ALL and by Martini et al. 2016 in CLL.
Our study was the first to assess cortactin in CML patients. Our study included 25 newly diagnosed CML chronic phase patients and 25 age and sex matched healthy controls.
Our study showed that cortactin levels significantly increased in patients group compared with control group (71.04 ± 20.04 in patients vs 36.8 ± 11.6 in controls. P <0.001).
Also, our study revealed a significant increase of cortactin levels in patients with no chr compared with patients with chr, thus, cortactin levels may predict remission in CML patients, so, cortactin could predict remission of CML patients.
We also revealed that cortactin levels were positively correlated with prognostic scores with high cortactin percent in patients with high risk scores.
Our study also revealed that cortactin levels were positively correlated with TLC and blast count at diagnosis and after 3 months of treatment, and negatively correlated with hemoglobin levels at diagnosis and after 3 months of treatment. So, cortactin may be related to tumor volume, patients with highest cortactin levels had large tumor volume.
We also validated a cutoff point equal or less than 73.8 % of cortactin for prediction of complete hematological remission in terms of sensitivity was 81.2% and specificity was 100%, positive predictive value was 100% and negative predictive value was 75%.