Change of the Notch1 Expression Level in Lymphoid Malignancies.

Abstract 4425

Notch gene family encodes single pass transmembrane receptors able to transducer intercellular signals involved in cell-fate determination. Notch signaling is the leading causes to the development of malignant tumors. Notch pathway plays a role in haematopoiesis affecting both stem cells and committed progenitors. The expression of Notch1 in thymic stromal cells and in developing thymocytes is consistent with Notch function. Notch1 is turn on before T-cell commitment along the lymphoid development; a variety of model systems indicates that Notch1 signaling is required for the earliest stages of T-cell commitment in the thymus and that, in its absence, cells develop toward the B-lineage. Overexpression of Notch1 gene was found in T-ALL, however, little is known the expression pattern of Notch1 gene in the different lymphoid malignancies. In the present study, the expression level of Notch1 gene was analyzed in patients with lymphoid malignancies. Real-time PCR with SYBR Green I technique was used for detecting Notch1 gene expression level in peripheral blood mononuclear cells of 43 patients with lymphoid malignancies [including 7 cases with T-ALL, 6 cases with T-NHL, 9 cases with B-ALL, 5 cases with B-CLL, 16 cases with B-NHL] and 20 healthy individuals. β2-microglobulin gene (β2M) was used as an endogenous reference. Relative changes in Notch1 gene expression level were used by the 2^-ΔCt×100% ×100% method. The expression level of Notch1 in both T-cell lymphoid malignancies group (Median: 0.897%) and B-cell lymphoid malignancies group (Median: 0.726%) was significant higher than those in the healthy control (Median: 0.288%) (P<0.01, P<0.01). Moreover, the expression level of Notch1 was different in the five types of lymphoid malignancies. That is, the highest in the B-CLL group, secondary in the T-NHL group, the lowest in the B-NHL group. And, it is not significant different between the B-NHL and healthy control groups. In conclusions, Overexpression of Notch1 gene was found not only in T-ALL, but also in T-NHL and B-cell leukemia and suggests that the abnormal overexpression pattern of Notch1 might play an important role in the pathogenesis of lymphoid malignancies. Down-regulation of Notch1 might be considered as target therapeutic strategy for lymphocytic malignancies.