Set7 Is Highly Expressed in B-Lineage Acute Lymphoblastic Leukemia Cells and Overexpression of Set7 Exhibits Antileukemia Effect

Set7 is a member of protein lysine methyltransferase family that is highly conserved in vertebrates. Set7 can regulate the maintenance of chromosome structure, cell cycle and apoptosis, and plays an important role in many kinds of cancer, metabolism and inflammatory process. However, studies concerning its pathogenic role in leukemia are scarce. We analyzed the expression of Set7 in different types of leukemia and healthy human bone marrow cells or peripheral blood from the Oncomine databases (http://www.oncomine.org), and showed that Set7 was highly expressed in acute lymphoid leukemia (ALL) patients, especially in patients with B-ALL. In this study, we examined the expression of Set7 in various hematopoietic tumor cell lines, bone marrow samples from patients and healthy volunteers. We found that Set7 was highly expressed in B-ALL cell lines Nalm6 and REH compared with other hematopoietic malignant cell lines. Furthermore, Set7 was overexpressed in bone marrow mononuclear cells of adult and pediatric patients with B-ALL than in healthy human bone marrow samples, and sorted CD19⁺ cells, as well (P<0.001). To investigate Set7 gene function, retroviral-mediated overexpression or removal experiments were performed. Gain-of-function and loss-of-function analyses in Nalm6 and REH cells demonstrated that Set7 inhibited cell growth, colony formation and enhanced the chemosensitivity of B-ALL cells to Vincristine (VCR), Arabinocytidine (Ara) and Daunorubicin (DNR). Protein sequence analysis showed that Ebf1 might be a potential substrate for Set7. The expression of Rad51 and Tnsf11, the downstream target genes of Ebf1, were changed as expected when Set7 was overexpressed in Nalm6 and REH. Our study shows for the first time that overexpression of Set7 has an inhibitory effect on B-ALL. These findings suggest that Set7 may be a promising molecular therapy target for B-ALL treatment and provide new clues for understanding the molecular mechanisms of the leukemogenesis of B-ALL.