Clinical study on deletion of IKZF1 gene in 93 children with B-cell acute lymphoblastic leukemia

Abstract

Objective To study the effect of IKZF1 gene deletion on the relapse and prognosis of children with B-cell acute lymphoblastic leukemia (B-ALL) , and provide a theoretical basis for the selection and intensity adjustment of chemotherapy in B-ALL children with IKZF1 gene. Methods From June 2014 to November 2016, a total of 93 children with B-ALL were included in the study. They were newly diagnosed in the Department of Hematology Oncology, Children′s Hospital of Kunming Medical University, and able to provide sufficient bone marrow DNA samples.They were divided into IKZF1 gene deletion group(n=18) and IKZF1 gene non-deletion group (n=75). The incidence of IKZF1 gene deletion was calculated. The gender, age, number of white blood cells count, early treatment response, central nervous system (CNS) classification, minimal residual disease(MRD) grouping, risk grouping, recurrence and survival constituent ratioes were compared between two groups. The 2-year disease-free survival (DFS) and overall survival(OS) rates of the two groups were calculated by Kaplan-Meier method, and the survival curves were plotted. The samples collection of this study were agreed from the guardians, and they signed the informed consent forms. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Kunming Medical University (approval No. CCLG-ALL-2015). Results ① The incidence of IKZF1 gene deletion was 19.4% (18/93). ② There were no significant differences in gender, age, CNS classification, early treatment response and risk grouping between the two groups (P>0.05). The proportion of children with white blood cell count ≥50×109/L and high-risk MRD in the IKZF1 gene deletion group were 38.9% (7/18) and 27.8% (5/18), respectively, which were significantly higher than those of IKZF1 non-deletion group with 13.3% (10/75) and 8.0% (6/75), respectively, and the differences were statistically significant (χ2=4.75, P=0.019; χ2=4.72, P=0.009). The recurrence rate of the IKZF1 gene deletion group was 33.3% (6/18), which was significantly higher than that of the IKZF1 non-deletion group with 9.3%(7/75), and the difference was also statistically significant (χ2=6.95, P=0.008). ③ The 2-year DFS and OS rates in the IKZF1 gene deletion group were (72.7±13.4)% and (81.8±11.6)%, respectively, which were significantly lower than those of IKZF1 non-deletion group with (92.3±3.0)% and (94.4±2.8)%, and the differences were significant (P<0.05). Conclusions Deletion of the IKZF1 gene is one of the high-risk predictors of recurrence in children with B-ALL. It should be used as a risk factor to guide the risk stratification of B-ALL children in order to adjust the intensity of chemotherapy method and improve their prognosis. Key words: Leukemia, B-cell; Gene deletion; Prognosis; Risk factors; IKZF1 gene; Child