Incorporation of long non-coding RNA expression profile in the 2017 ELN risk classification can improve prognostic prediction of acute myeloid leukemia patientsResearch in context
Cheng-Hong Tsai,
Chi-Yuan Yao,
Feng-Min Tien,
Jih-Luh Tang,
Yuan-Yeh Kuo,
Yu-Chiao Chiu,
Chien-Chin Lin,
Mei-Hsuan Tseng,
Yen-Ling Peng,
Ming-Chih Liu,
Chia-Wen Liu,
Ming Yao,
Liang-In Lin,
Wen-Chien Chou,
Chien-Yu Chen,
Hsin-An Hou,
Hwei-Fang Tien
Affiliations
Cheng-Hong Tsai
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan
Chi-Yuan Yao
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Feng-Min Tien
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Jih-Luh Tang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
Yuan-Yeh Kuo
Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
Yu-Chiao Chiu
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Chien-Chin Lin
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Departments of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Mei-Hsuan Tseng
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Yen-Ling Peng
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Ming-Chih Liu
Pathology, National Taiwan University Hospital, Taipei, Taiwan
Chia-Wen Liu
Pathology, National Taiwan University Hospital, Taipei, Taiwan
Ming Yao
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Liang-In Lin
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
Wen-Chien Chou
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Departments of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Chien-Yu Chen
Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan; Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan
Hsin-An Hou
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Correspondence authors.
Hwei-Fang Tien
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Correspondence authors.
Background: Expression of long non-coding RNAs (lncRNAs) has recently been recognized as a potential prognostic marker in acute myeloid leukemia (AML). However, it remains unclear whether incorporation of the lncRNAs expression in the 2017 European LeukemiaNet (ELN) risk classification can further improve the prognostic prediction. Methods: We enrolled 275 newly diagnosed non-M3 AML patients and randomly assigned them to the training (n = 183) and validation cohorts (n = 92). In the training cohort, we formulated a prognostic lncRNA scoring system composed of five lncRNAs with significant prognostic impact from the lncRNA expression profiling. Findings: Higher lncRNA scores were significantly associated with older age and adverse gene mutations. Further, the higher-score patients had shorter overall and disease-free survival than lower-score patients, which were also confirmed in both internal and external validation cohorts (TCGA database). The multivariate analyses revealed the lncRNA score was an independent prognosticator in AML, irrespective of the risk based on the 2017 ELN classification. Moreover, in the 2017 ELN intermediate-risk subgroup, lncRNA scoring system could well dichotomize the patients into two groups with distinct prognosis. Within the ELN intermediate-risk subgroup, we found that allogeneic hematopoietic stem cell transplantation could provide better outcome on patients with higher lncRNA scores. Through bioinformatics approach, we identified high lncRNA scores were correlated with leukemia/hematopoietic stem cell signatures. Interpretation: Incorporation of lncRNA scoring system in 2017 ELN classification can improve risk-stratification of AML patients and help clinical decision-making. Fund: This work was supported Ministry of Science and Technology, and Ministry of Health and Welfare of Taiwan. Keywords: lncRNA, AML, Risk stratification, Prognostication
