Genetic heterogeneity in core-binding factor acute myeloid leukemia and its clinical implication
Objective:To explore the genetic heterogeneity and prognostic factors in adult core-binding factor acute myeloid leukemia(CBF-AML).Methods:The clinical data of 271 newly diagnosed adult CBF-AML were retrospectively analyzed,including 188 patients with t(8;21)AML and 83 patients with inv(16)/t(16;16)AML.Chi-square test was used to compare the difference of molecular genetic between t(8;21)AML and inv(16)/t(16;16)AML.Log-rank test and Cox regression model were used to analyze the impact of clinical factors and gene mutations on survival and relapse in CBF-AML.Results:Sex chromosome deletion,CD19 expression,and CD56 expression were more common in t(8;21)AML(33.6％vs 1.5％,P＜0.001;58.9％vs 6.8％,P＜0.001;63.8％vs 1.7％,P＜0.001),while trisomy 22 was more common in inv(16)/t(16;16)AML(13.6％vs 0.7％,P＜0.001).The incidences of KIT and EZH2 mutations in t(8;21)AML were significantly higher than those in inv(16)/t(16;16)AML(51.8％vs 28.3％,P=0.010;18.8％vs 4.3％,P=0.022).The incidences of FLT3 and WT1 mutations were significantly higher in inv(16)/t(16;16)AML than those in t(8;21)AML(34.8％vs 12.9％,P=0.003;15.2％vs 4.7％,P=0.044).Fort(8;21)AML patients,KIT D816 was an independent risk factor for overall survivai(P=0.050)and allogeneic hematopoietic stem cell transplantation was an independent protective factor for overall survival(P=0.029).Higher bone marrow blasts and CD19 negative were independent risk factors for event-free survival(P=0.043;P=0.008).KIT D816 and CD19 negative were independent risk factors for cumulative incidence of relapse(P=0.014;P=0.036).For inv(16)/t(16;6)AML patients,extramedullary involvement was the independent risk factor for event-free survival(P=0.023)and allo-geneic hematopoietic stem cell transplantation was the independent protective factor for cumulative incidence of re-lapse(P=0.037)and event-free survival(P=0.015).Conclusion:t(8;21)and inv(16)/t(16;16)AML are het-erogeneous in clinical characteristics,cytogenetics,gene mutation profile,and prognostic factors.
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