In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-11-18)
Abstract:
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 (R 2 = 0.74, P 〈 5.4e−05). A decision tree analysis, based on 3-log reduction of RUNX1 - RUNX1T1 and c KIT -D816 mut 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-020-76933-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2615211-3
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