The emerging role of NOTCH target genes in Egyptian childhood acute lymphoblastic leukemia

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.

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 real-time polymerase chain reaction (qRT-PCR).

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, 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.

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.