| Objective:Some studies found that dysregulated Notch signaling correlated with the tumorigenesis and development. Notch1 protein widely expressed in human solid tumors and became a hot-spot in the field of cancer research as a new target to treat the tumors. Despite a greate improvement in the clinical efficacy of treating childhood acute leukemia at present, there were still 30% of cases suffering poor response to chemotherapy. Information about the expression of Notch1 in pediatric acute leukemia is less in China.The purpose of this study was to investigate the expression of Notch1 protein in the bone marrow cells of acute leukemia in children and detect a relationship with immunophnotypes, the clinical classifications, therapeutic effects and early prognosis of acute leukemia, and to explore the role of Notch1 in the tumorigenesis and progression of acute leukemia, accordingly to provide a reasonable therapeutic strategies for treatment of acute leukemia.Methods:1. Immunophenotype of leukemic cells was performed by three labelling flow cytometry.2. The expression of Notch1 at the protein level and its location were examined by immunohistochemical assay in 49 cases with newly diagnosed pediatric acute leukemia and 20 cases with non-malignant hematologic disease bone marrow cells.Results: 1. 49 children with acute leukemia included 29 cases of B-ALL, 9 cases of T-ALL, 11 cases of ANLL (M1 2 cases, M2 6 cases, M3 3cases).2. Notch1 protein in AL bone marrow cells mainly expressed in the cytoplasm and less in nucleus. Notch1 protein expression in AL (23/49, 46.9%) bone marrow cells was significantly higher than that in the control group (3/20, 15.0%) (P<0.05). The positive rates of Notch1 expression in the T-ALL group (7/9, 77.8%), ANLL group (7/11, 63.6%) were obviously higher than the control group (3/20, 15%) with significant difference (P<0.05). Compared with T-ALL group and ANLL group, the expression of Notch1 protein decreased in B-ALL group. The positive rates of the expression of Notch1 protein in B-ALL group and control group were 31.0%, 15.0%, respectively, which did not differ statistically (P>0.05). Immunohistochemistry results showed the frequency of Notch1 protein expression of B-ALL group (9/29, 31.0%) was considerably lower than T-ALL group (7/9, 77.8%) (P<0.05). The difference between ALL and ANLL is indistinctive (P>0.05).3. The positive expression rate of Notch1 protein in children ALL with the high risk(HR) group, moderate risk(MR) group, low risk(LR) group were 52.9%, 36.4%, 30.0%, respectively, there were not significance (P>0.05).4. In acute leukemia cases, there was no correlation between the expression of Notch1 proerin and remission induction treatment effect. In contrast, in B-ALL patients with more than 6 months follow-up, Notch1 expression rates in the favorable group(complete remission without relapse) and the unfavorable group(death or relapse) were 21.4%, 80.0% respectively (P<0.05).Conclusions:1. The expression level of Notch1 in children AL was abnormal suggesting that it may play an important role in the tumorgenesis and progression of pediatric acute leukemia. Notch1 protein expression in ALL associate with immunophenotypes, the expressive level in T-ALL was significant higher than that of B-ALL. 2. Though the expression of Notch1 protein in B-ALL was not high, it may be a poor prognosis factor. |
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