The emerging role of NOTCH target genes in Egyptian childhood acute lymphoblastic leukemia
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memo https://doi.org/10.1007/s12254-020-00665-2
The emerging role of NOTCH target genes in Egyptian childhood acute lymphoblastic leukemia Mona Reyad · Sherin Abdel-Aziz · Layla M. Saleh · Samah El-Ghlban · Ibrahim El Tantawy El Sayed · Hasan Abdel-ghaffar
Received: 5 September 2020 / Accepted: 28 October 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Summary Background Acute lymphoblastic leukemia (ALL), characterized by overproduction and accumulation of immature lymphoid cells in bone marrow and peripheral blood, is the most common malignancy in children. NOTCH signaling is suggested to be a key event in hematological malignancies and appears to be a major oncogenic trigger in leukemia. Several studies on NOTCH target gene (HES-1, p21 and c-Myc) expression evaluated the correlation between these genes in AML (acute myeloid leukemia), but this relationship has not yet been clarified in ALL. Therefore, we aimed to study the expression of these genes in our Egyptian patients with ALL to obtain more information. Patients and methods RNA was extracted from peripheral blood mononuclear cells (PBMNCs) of 91 pediatric ALL patients (49 B-cell acute lymphoblastic leukemia [B-ALL] and 42 T-cell acute lymphoblastic leukemia [T-ALL]) and 52 healthy controls. The expression levels were determined by quantitative realtime polymerase chain reaction (qRT-PCR). Results Median p21 and HES1 expressions were down regulated, while c-Myc expression was up-regulated in B-ALL cases (p < 0.001, p = 0.008, p < 0.001, respectively) and in T-ALL cases (p = 0.049, p = 0.015, p < 0.001, respectively) when compared to the control group. Median HES1 expression was down regulated, M. Reyad () · S. El-Ghlban · I. El Tantawy El Sayed Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Menoufia, Egypt [email protected] S. Abdel-Aziz · L. M. Saleh · H. Abdel-ghaffar Hematology section, Oncology Center Mansoura University, Mansoura, Egypt Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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in B-ALL cases compared to T-ALL cases (p = 0.002), while P21 and c-Myc did not differ significantly between B-ALL and T-ALL cases. Conclusion P21 expression showed a significant positive correlation with HES1 expression and c-Myc showed nonsignificant negative correlations with p21 and HES1, thus, suggesting that HES1 may affect ALL cells through the HES1–p21 pathway. Patients with over expressed c-Myc had worse survival than patients with low expression which suggested it is a risk predictor. Keywords HES1 · P21 · c-Myc · T-ALL · Expression level
Introduction Acute lymphoblastic leukemia (ALL) is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells, resulting in a marked decrease in normal blood cell production [1]. ALL constitutes 30% of all pediatric malignancies and 70% of pediatric leukemia; cases show a male to female ratio of 2.3:1. The 2–10 year age group constitutes 68.5% [2]. N
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