定量多色FISH检测儿童ETV6-RUNX1阳性急性淋巴细胞白血病的异质性及克隆演化

OBJECTIVE: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1(+) acute lymphoblastic leukemia (ALL) in China. METHODS: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1(+) ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range), count data were shown with percent (%). Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1(+) ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. CONCLUSION: The clone evolution was detected in pediatric ETV6-RUNX1(+) ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.