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العنوان
Detection of Cancer-Testis Antigens Genes in Acute Myeloid Leukemia Patients /
المؤلف
Abd EI-Hafez, Mohammed Ahmed Mohammed.
هيئة الاعداد
باحث / Mohammed Ahmed Mohammed Abd EI-Hafez
مشرف / Ibrahim Mohammed Baghdadi
مشرف / Ali Zaky Glal
مشرف / Sabry Abd Allah Shoeab
الموضوع
Blood - Diseases. Internal medicine. Leukemia. Hematologic Neoplasms.
تاريخ النشر
2013.
عدد الصفحات
234 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الطب الباطني
تاريخ الإجازة
10/4/2013
مكان الإجازة
جامعة المنوفية - كلية الطب - internal medicine.
الفهرس
Only 14 pages are availabe for public view

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from 234

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed ( Lin and Levy., 2012). Cancer-testis (CT) antigens/genes show restricted expression in normal tissues but widespread expression in many tumour types.This, coupled with their ability to induce cytotoxic T-lymphocyte responses, makes them attractive vaccine candidates (Liggins et al., 2010). PASD1 [Per ARNT Sim (PAS) Domain containing protein 1] is a member of the CT-X group of CTAs (Scanlan et al., 2004). The PASD1 gene maps to the q28 region of chromosome X. PASD1 is a 733 amino acid nuclear protein that contains one PAS domain. The PASD1-predicted protein is suggested to encode a transcription factor (Liggins et al., 2004a). PASD1 can stimulate autologous T-cell responses, and it is therefore considered to be a potential immunotherapeutic target for the treatment of various malignancies, including DLBCL and AML (Liggins et al., 2010). The aim of the work is to detect the expression of PASD1 gene in patients with AML and its relation with clinical features and CR of AML. To achieve such target,we selected 60 patients with AML and 30 healthy age and sex matched controls.They were divided into two main groups, group І included 60 AML patients (25 males and 35 females), all of them performed blood film & BM examination , immunophenotyping, cytogenetics study by G-banding on BM samples and RT-PCR analysis of PASD1 gene on peripheral blood sample (or bone marrow sample), and group II included 30 healthy control (14 males and 16 females) , all of them performed CBC ,blood film and RT-PCR analysis of PASD1 gene on peripheral blood sample. The group I (AML patients) was then divided into two subgroups according to PASD1 expression which were PASD1 positive subgroup (12 patients) and PASD1 negative subgroup (48 patients). We found that there was no significant difference among the studied groups as regard age and gender (P>0.05). As regard to the expression of PASD1 gene in the studied groups, we found that the expression of PASD1 in group І (AML patients) ( 12 out of 60 =20%) is stastically significant as compared to group II (PASD1 was not expressed ) (p –value <0.05). As regards to the distribution of the studied PASD1 among AML patients (group I) according to the gender , there was no significant difference (p –value >0.05). As regards to the distribution of the studied PASD1 among AML patients (group I) according to the age , 66.7% (8 out of 12) of the PASD1 positive subgroup were < 45 years old and 29.2% (14 out of 48) of the PASD1 negative subgroup were < 45 years old.This difference was statistically significant (p –value <0.05). As regard to the occurrence of fever in PASD1 positive and PASD1 negative AML subgroups,we found that PASD1 positive AML patients (3 out of 12=25%) had less fever at presentation when compared to PASD1 negative AML patients (29 out of 48=60.4%). This difference was statistically significant (p –value <0.05). As regard to other clinical data at presentation, our study did not find significant relation between PASD1 expression in AML patients and the presence of bleeding tendency ,splenomegaly, hepatomegaly and lymphadenopathay at presentation (p –value >0.05). As regard to the hematological variables at presentation, our study found no significant relation between PASD1 expression and any of the measured hematological variables (Hb, platelet count, WBCs count, PT, INR, PTT, fibrinogen level and FDPs) (p –value >0.05). As regard to the distribution of the morphological subtypes .