Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide
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
Affiliations
Yang Shen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Ya-Kai Fu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Yong-Mei Zhu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Yin-Jun Lou
Zhejiang Institute of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine Peking, China
Zhao-Hui Gu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Jing-Yi Shi
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Bing Chen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Chao Chen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Hong-Hu Zhu
Peking University People's Hospital, China
Jiong Hu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Wei-Li Zhao
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Jian-Qing Mi
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Li Chen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Hong-Ming Zhu
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Zhi-Xiang Shen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Jie Jin
Zhejiang Institute of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine Peking, China
Zhen-Yi Wang
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Jun-Min Li
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Zhu Chen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
Sai-Juan Chen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine and Collaborative Innovation Center of Systems Biomedicine, SJTU, Shanghai, China
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.