Integrating resistance functions to predict response to induction chemotherapy in de novo acute myeloid leukemia. (20th August 2019)

• Record Type: Journal Article
• Authors: Chiu, Yu‐Chiao; Hsiao, Tzu‐Hung; Tsai, Jia‐Rong; Wang, Li‐Ju; Ho, Tzu‐Chieh; Hsu, Shih‐Lan; Teng, Chieh‐Lin Jerry
• Is Part Of: European journal of haematology. Volume 103:Number 4(2019)
• Page Start: 417
• Page End: 425
• Publication Date: 2019-08-20
• Subjects: acute myeloid leukemia -- chemosensitivity -- induction chemotherapy -- prediction model -- resistance functions; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13301
• Languages: English
• ISSNs: 0902-4441

Abstract

Abstract: Objectives: This study explored resistance functions and their interactions in de novo AML treated with the "7 + 3" induction regimen. Methods: We analyzed RNA‐sequencing profiles of whole bone marrow samples from 52 de novo AML patients who completed the "7 + 3" regimen and stratified patients into CR (n = 35) and non‐CR (n = 17) groups. Results: A systematic gene set analysis revealed significant associations between chemoresistance and mTOR ( P < .001), myc ( P < .001), mitochondrial oxidative phosphorylation ( P < .001), and stemness ( P = .002). These functions were independent with regard to gene contents and activity scores. An integration of these four functions showed a prediction of chemoresistance (area under the receiver operating characteristic curve = 0.815) superior to that of each function alone. Moreover, our proposed seven‐gene scoring system significantly correlated with the four‐function model ( r = .97; P < .001) to predict chemoresistance to the "7 + 3" regimen. On multivariate analysis, a seven‐gene score of ≥−0.027 (hazard ratio: 11.18; 95% confidence interval: 2.06‐60.65; P = .005) was an independent risk factor for induction failure. Conclusions: Myc, OXPHOS, mTOR, and stemness were responsive for chemoresistance in AML. Treatments other than the "7 + 3" regimen need to be considered for de novo AML patients predicted to be refractory to the "7 + 3" regimen.