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RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia

 TaeHyung Kim  ;  Joon Ho Moon  ;  Jae-Sook Ahn  ;  Seo-Yeon Ahn  ;  Sung-Hoon Jung  ;  Deok-Hwan Yang  ;  Je-Jung Lee  ;  Myung-Geun Shin  ;  Seung Hyun Choi  ;  Ja-Yeon Lee  ;  Marc S Tyndel  ;  Hui Young Lee  ;  Kyoung Ha Kim  ;  Yu Cai  ;  Yoo Jin Lee  ;  Sang Kyun Sohn  ;  Yoo Hong Min  ;  June-Won Cheong  ;  Hyeoung-Joon Kim  ;  Zhaolei Zhang  ;  Dennis Dong Hwan Kim 
 SCIENTIFIC REPORTS, Vol.10(1) : 20119, 2020-11 
Journal Title
Issue Date
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Core Binding Factor Alpha 2 Subunit / genetics ; Core Binding Factors / genetics* ; Female ; Gene Expression Regulation, Leukemic ; Gene Rearrangement ; Humans ; Leukemia, Myeloid, Acute / genetics* ; Leukemia, Myeloid, Acute / mortality ; Leukemia, Myeloid, Acute / pathology* ; Male ; Middle Aged ; Mutation* ; Myosin Heavy Chains / genetics ; Neoplasm, Residual / genetics ; Oncogene Proteins, Fusion / genetics ; Prognosis ; Proof of Concept Study ; RUNX1 Translocation Partner 1 Protein / genetics ; Sequence Analysis, RNA / methods* ; Young Adult
DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P < 6.3e-05 and P < 2.2e-13). The level of reduction of RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R2 = 0.74, P < 5.4e-05). A decision tree analysis, based on 3-log reduction of RUNX1-RUNX1T1 and cKIT-D816mut at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P < 0.08) and 2-year relapse incidence rates at 13%, 42%, and 67% (P < 0.05). On the other hand, although low residual allelic burden was common, it was not associated with long-term outcome, indicating that mutation clearance alone cannot be interpreted as MRD-negative. Overall, our study demonstrates that the clinical utility of RNA sequencing as a potential tool for MRD monitoring in fusion gene-driven AML such as RUNX1-RUNX1T1 AML.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
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