Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide

oleh: Yang Shen, Ya-Kai Fu, Yong-Mei Zhu, Yin-Jun Lou, Zhao-Hui Gu, Jing-Yi Shi, Bing Chen, Chao Chen, Hong-Hu Zhu, Jiong Hu, Wei-Li Zhao, Jian-Qing Mi, Li Chen, Hong-Ming Zhu, Zhi-Xiang Shen, Jie Jin, Zhen-Yi Wang, Jun-Min Li, Zhu Chen, Sai-Juan Chen

Format: Article
Diterbitkan: Elsevier 2015-06-01

Deskripsi

Background: Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL. Methods: We included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or -TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2. Results: More high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease-free survival in both training (HR = 6.761, 95% CI 2.179–20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089–14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS. Conclusion: In an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL.