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Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemi

Authors
 JinJuKim  ;  JiEunJang  ;  HyeonAhLee  ;  MiRiPark  ;  HyeWonKook  ;  Seung-TaeLee  ;  JongRakChoi  ;  YooHongMin  ;  SaeamShin  ;  June-WonCheong 
Citation
 ANNALS OF LABORATORY MEDICINE, Vol.43(4) : 328-336, 2023-07 
Journal Title
ANNALS OF LABORATORY MEDICINE
ISSN
 2234-3806 
Issue Date
2023-07
MeSH
Hematopoietic Stem Cell Transplantation* ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute* / diagnosis ; Leukemia, Myeloid, Acute* / genetics ; Neoplasm, Residual / diagnosis ; Neoplasm, Residual / genetics ; Recurrence
Keywords
Acute myeloid leukemia ; High-throughput nucleotide sequencing ; Minimal residual disease
Abstract
Background: AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]<5%). This study aimed to develop a targeted next-generation sequencing (NGS) panel to detect MRD in AML patients and validate its performance.

Methods: We designed an error-corrected, targeted MRD-NGS panel without using physical molecular barcodes, including 24 genes. Fifty-four bone marrow and peripheral blood samples from 23 AML patients were sequenced using the panel. The panel design was validated using reference material, and accuracy was assessed using droplet digital PCR.

Results: Dilution tests showed excellent linearity and a strong correlation between expected and observed clonal frequencies (R>0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival.

Conclusions: Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.
Files in This Item:
T202302988.pdf Download
DOI
10.3343/alm.2023.43.4.328
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kook, Hye Won(국혜원)
Kim, Jin Ju(김진주) ORCID logo https://orcid.org/0000-0001-9166-1848
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Jang, Ji Eun(장지은) ORCID logo https://orcid.org/0000-0001-8832-1412
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195354
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