Application value of quantitative monitoring of RUNX1-RUNX1T1 fusion gene in pediatric acute myeloid leukemia

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Objective To explore the prognostic value of quantitative monitoring of RUNX1-RUNX1T1 fusion gene in pediatric t(8; 21)/RUNX1-RUNX1T1 positive acute myeloid leukemia (AML). Methods A total of 81 newly diagnosed AML children with t (8; 21)/RUNX1-RUNX1T1 positive were enrolled in the People′s Hospital, Peking University, between August 2005 and January 2016.RUNX1- RUNX1T1 gene copy number of all the patients was analyzed by real-time quantitative PCR (qPCR) technology at diagnosis and after therapy in all patients.Cumulative incidence of relapse rate (CIR), event-free survival (EFS) rate and overall survival (OS) rate were estimated by Kaplan-Meier method and prognostic factors were evaluated by COX regression. Results The level of RUNX1-RUNX1T1 gene on diagnosis was used as the baseline to determine whether the level of gene after treatment had a more than 3 logarithmic (3 log) reduction.After 2 courses of induction therapy, the patients with a more than 3 log reduction of RUNX1-RUNX1T1 transcript levels(≥3 log)had better EFS rate (82.4% vs.57.6%, χ2=7.454, P<0.01), and better OS (93.6% vs.59.3%, χ2=9.703, P<0.01), compared to the patients with a less than 3 log reduction(<3 log). Multivariate analysis showed that 3 log reduction in RUNX1- RUNX1T1 transcript levels after 2 courses of induction therapy was an independent prognostic factor for EFS rate [hazard ratio(HR)=4.223, 95% confidence interval(CI): 1.507-11.836, P<0.01]and OS rate (HR=5.002, 95%CI: 1.282-19.516, P<0.05). When periodically monitoring the RUNX1-RUNX1T1 gene, 63 out of the 81 children patients were monitored for more than 6 times.The patients who had a more than 3 log reduction of gene before, but then those whose gene transcript level rose more than 1 log level were divided into group A, and the remaining patients were divided group B, and the difference of CIR was statistically significant between group A and group B (46.7% vs.4.7%, P<0.01). Conclusions RUNX1-RUNX1T1 gene copy number was detected with qPCR method in pediatric t(8; 21)/RUNX1-RUNX1T1 positive AML, which can determine the treatment effect, predict the recurrence of patients and assess long-term prognosis.Thus it has great clinical application value. Key words: Leukemia, myeloid, acute; Gene fusion, RUNX1-RUNX1T1 fusion gene; Neoplasm, residual; Survival analysis; Child