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العنوان
Evaluation of New Markers for Minimal Residual Disease in Precursor B Acute Lymphoblastic Leukemia /
المؤلف
Morcos, Maureen Raafat Farag.
هيئة الاعداد
باحث / مورين رأفت فرج
مشرف / رانية محمد بكرى
مناقش / ماجد صلاح
مناقش / عبير مختار
الموضوع
Lymphoblastic Leukemia.
تاريخ النشر
2022.
عدد الصفحات
122 p . ;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب (متفرقات)
الناشر
تاريخ الإجازة
29/8/2021
مكان الإجازة
جامعة أسيوط - كلية الطب - Clinical Pathology Department
الفهرس
Only 14 pages are availabe for public view

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from 138

Abstract

On the contrary of our results, (Tang et al., 2015) studied the frequency of expression of CD66c in adult B-ALL (n = 43; male n = 20; female n =23 with a median age of 38 y) and its potential correlation to the BCR-ABL1 fusion gene expression. They found that overexpression of CD66c was observed in 35/43 cases (81.4%). They confirmed the stable expression of CD66c and recommended its use in recognition of abnormal leukemia cells at primary diagnosis and in monitoring of MRD during treatment. Also, (Jain et al., 2018) analysed 73 cases (median age 22y), (33 males and 40 females) for the expression of CD66c where overexpresion was observed in 52.17% of cases. These differences may be explained by different age groups between our study and these studies as well as female predominance in these studies compared to male predominance in our study (60%).In our study, CD123 overexpression was observed in number of cases (55%) with mean value 31.18% ± 30.86% and median value 26.4% ranging from 0.02% to 89%. In agreement with our results, (Coustan-Smith et al., 2011) searched for new markers of MRD in B- ALL pediatric patients by defining differences in genome-wide gene expression between leukemic and normal cells. Among genes differentially expressed by genome-wide expression array analysis, they selected 30 markers for further studies based on their highly abnormal expression at the mRNA level in ALL cases and on the availability of specific Abs suitable for routine flow cytometric studies. They found that 22 of the 30 markers were also differentially expressed by flow cytometry. The top 16 differentially expressed markers listed in were included (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99 and CD300A). They observed CD 123 overexpression in (50.7%) of cases. Regarding higher level of expression compared to our study, (Patkar et al., 2012) studied B-ALL cases in India for MRD testing. The antibodies used included CD45, CD11a, CD38, CD20, CD10, CD19, CD58, CD34, CD123, and CD22. They evaluated eight cases and found that overexpression of CD123 was seen in 75% of cases. The different level of expression may be due to ethnic variability and low number of patients in their study. CD34: In our study, CD34 overexpression was observed in number of cases (67.5%) with mean value 38.48% ± 29.65% and median value 47.8% ranging from 0.4% to 81.5%. As in our analysis, (Pui et al., 1993) tested 335 pediatric ALL cases for the clinical Significance of CD34 expression and found that CD34 antigen was expressed in 235 (70%) of casesLevel of expression of markers at post-induction phase: At post induction phase, markers were evaluated for the stability of their surface expression from diagnosis to relapse. This means that no complete loss or gain of markers could be found. At post induction phase, CD66c showed highest stability as cases with overexpression were 12 out of 28 positive cases at diagnosis (42.9%). Also, the mean value for CD66c in patients in CR was 35.01% ±32.31% in comparison to 47.89% ±32.62% in relapsed patients (p<0.05). In agreement with our results, (Jain et al., 2018) studied twelve cases post induction bone marrow aspirate samples and analysed them for the stability of CD66c and they were found to be stably expressed. Also, (Kalina et al., 2005) followed up 39 childhood cases from diagnosis to relapse and concluded that CD66c expression stays qualitatively stable from diagnosis to relapse in all relapsed cases studied. This finding together with high frequency of CD66c positive cases can support inclusion of CD66c into panels for MRD detection in patients positive for this marker at diagnosis. CD73: In a descending order, CD73 showed less stability as we observed that cases with overexpression were 6 out of 28 positive cases at diagnosis (21.4%). Also, the mean value for CD73 in patients in CR was 28.92% ±20.55% in comparison to 33.07% ±29.61% in relapsed patients (p < 0.05) showing the stability of marker. In concordance to our results, (Tembhare et al., 2018) studied post induction stability of CD73 in 24 cases and found that CD73 was one of the highest markers showing over expression at post induction. CD123: CD123 showed least stability as we observed that cases with overexpression were 2 out of 22 positive cases at diagnosis (9%). Also, the mean value for CD123 in patients in CR was 29.91% ±30.64% in comparison to 34.55% ±32.68% in relapsed patients (p<0.05). (Jain et al., 2018) studied twelve cases post induction bone marrow aspirate samples and confirmed the stability of CD123. CD34: At post induction phase, CD34 showed that cases with overexpression were 4 out of 27 positive cases at diagnosis (14.8%). Also, the mean value for CD34 in patients in CR was 30.02% ±25.49% in comparison to 60.77% ±29.23% in relapsed patients (P= 0.00). In agreement with our study, (Jiang et al., 2016) concluded that CD34 pattern in B-ALL cannot be used as specific surface marker. However, CD34 can serve as specific biomarker for prognosis. Lack of CD34 expression is associated with favorable prognosis. Correlations between markers and overall survival: CD73: We found no significant difference between low and high level of expression of CD73 regarding OS. In agreement with our results, (Gao et al., 2014) reported that CD73 expression had no prognostic value in children (1–18 years old) with acute lymphoblastic leukemia that underwent the study (n= 338). CD66c: Also, we found no significant difference between low and high level of expression of CD66c regarding OS in agreement with (Ismail et al., 2017) where their study included 33 newly diagnosed B-ALL cases of both sexes. The median follow-up period for B-ALL cases in their study was 31.8 weeks and they found no significant correlation between OS and CD66c. CD123: We found no significant difference between low and high level of expression of CD123 regarding OS in disagreement with (Liu et al., 2019) who showed that abnormal CD123 expression was negatively correlated with OS and this may be due to demographic variability between China and Egypt and also low number of patients in our study who showed CD123 overexpression at the post induction phase (n=2). CD34: Also, no significant difference was found between low and high level of expression of CD34 regarding OS. In disagreement with our results, (Jiang et al., 2016) observed that CD34 was more expressed in poor-risk B-ALL adult patients and lack of CD34 is associated with better overall survival rates. The difference may be due to inclusion of children and adults in our studied participants with the majority of our patients were children (88.3%).