Ik6 expression provides a new strategy for the therapy of acute lymphoblastic leukemia

Abstract

Our previous study demonstrated that the dominant-negative Ikaros isoform 6 (Ik6) is overexpressed in Chinese children with newly diagnosed B-acute lymphoblastic leukemia (B-ALL) and is strongly associated with a poor outcome. The purpose of the present study was to further explore the function of Ik6 in B-ALL. The association between Ik6 expression as detected by real-time PCR and efficacy of chemotherapy was evaluated. The effect of the alteration in Ik6 on leukemic cell lines was assessed by in vitro gain-of-function and loss-of-function techniques. PCR analysis showed that Ik6 expression was decreased when patients completed induction chemotherapy and reached complete remission. Ik6 expression was significantly increased when patients suffered relapse. Stable transfection of Ik6 into the Nalm-6 cell line revealed that Ik6 enhanced proliferation of Nalm-6 cells through the promotion of G0/G1-to-S-phase transition and enhanced chemoresistance to chemotherapeutics through anti-apoptotic effects. However, Ik6 expression did not affect the invasion of Nalm-6 cells. In contrast, silencing of Ik6 in Sup-B15 cells significantly inhibited proliferation and increased chemosensitivity. The present study suggests that Ik6 may be a biological marker of chemosensitivity and relapse and Ik6 may provide a potential therapeutic strategy for ALL.