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العنوان
Expression of lymphoid enhancer factor 1 (LEF1) in adult patients with b-precursor acute lymphoblastic leukemia as a prognostic marker in comparison to other prognostic markers/
المؤلف
Youssef, Sara Mostafa Ahmed.
هيئة الاعداد
باحث / سارة مصطفي أحمد يوسف
مناقش / نادية على صادق
مناقش / اكرم عبد المنعم دغيدى
مشرف / منى وجدى عياد
مشرف / أميرة إبراهيم فياض
مشرف / منال عبد الستار الصردي
الموضوع
Clinical Pathology. lymphoblastic leukemia.
تاريخ النشر
2017.
عدد الصفحات
80 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب (متفرقات)
تاريخ الإجازة
4/1/2017
مكان الإجازة
جامعة الاسكندريه - كلية الطب - Clinical and Chemical Pathology
الفهرس
Only 14 pages are availabe for public view

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Abstract

Acute lymphoblastic leukemia is a malignant neoplasm of the lymphocyte precursor cells. ALL represents approximately 25% of all childhood cancers and less than 1% of adult cancers. Long term survival rates for adult ALL have not significantly improved over the past two decades; the five year survival is still 30-40% for patients aged 20-60 years, 15% for those older than 60 and less than 5% for patients older than 70 years. Unlike the cure rate in childhood leukemia, only 20-40 % of adults with ALL are cured with current treatment regimens.
The diagnosis of ALL requires examination of peripheral blood samples and bone marrow aspirates. Such examination involves morphology under light microscopy, cytochemistry, immunophenotyping, cytogenetic studies and molecular genetic analysis. Based on retrospective analysis of large cohorts of patients, conventional pre-therapeutic risk criteria, including age, elevated white blood cell count at diagnosis, adverse immunophenotypic features, cytogenetic and molecular aberrations provide the basis for risk stratification in current treatment protocols.
Lymphoid enhancing factor1 is a key mediator of the canonical Wingless-type (Wnt) pathway activation results in the accumulation of B-catenin, which translocate to the nucleus and forms a complex with LEF/T-cell factor DNA binding proteins, thereby enhancing the transcription of target genes including; MYC, CyclinD1 Wnt downstream target genes which involved in the regulation of central cellular processes, such as differentiation, cell cycle, proliferation, and survival.
Fifty subjects were recruited in this study; twenty five adult patients with de novo acute lymphoblastic leukemia (ALL) admitted to hematology unit of Alexandria University and twenty five subjects of matched age and sex served as control group. All patients were subjected to full history taking, complete clinical examination, and abdominal ultrasonography. Laboratory investigations were done including CBC, liver function tests, renal function tests, and CSF cytology. In addition to Bone marrow aspirate examination and cytochemistry, Immunophenotyping by flow cytometry and Quantitative real-time RT-PCR for LEF1 gene fold expression.
The present study aimed to assess the correlation between the expression of the LEF1 gene expression and prognosis in adult patients with acute lymphoblastic leukemia (ALL) at day 28 after receiving induction chemotherapy and after 6 months follow up period.
Twenty five adult patients including 15 males and 10 females were classified to risk groups according to GMALL risk stratification to; standard risk group (11 patients), high risk group (12 patients), very high risk group (8%).According to immunophenotyping results there were ;common B-ALL which was the most encountered type(64%) , followed by pro-B(24%) and pre-B(12%).
Regarding clinical treatment outcome after day 28 induction chemotherapy; twenty one patients were achieved CR and only 2 cases were refractory. After 6 months follow up period 18 patients continued in CR while 5 patients were relapsed and 2 patients were refractory.
In current study relation between patients and controls regarding LEF1 gene expression was done. There was a significant statistical difference between patients and controls regarding LEF1 gene expression.
Patients were classified according to LEF1gene expression to quartiles (Q1-Q4) where Q4 contained the upper 25 percent as high LEF1 gene expression and Q1-Q3 contained low LEF1 gene expression.
Correlations between LEF1 gene expression and clinical, laboratory, immunophenotypic subtypes and risk categorization showed no significant statistical difference .There was a significant statistical difference between LEF1 gene expression and BCR-ABL.
Patients were classified according to clinical outcome to remission and non-remission. On comparing between LEF1 gene expression and prognostic variables regarding treatment outcome, LEF1 was the only predictable prognostic variable which showed a significant statistical difference denoting that it might be used as an independent prognostic factor to assess poor outcome in adult B-ALL patients.