인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Minimal/measurable residual disease (MRD) in Acute Myeloid Leukemia (AML) is defined as persistent leukemic cells below cytomorphological detection threshold. Next generation sequencing (NGS) of circulating cell-free DNA (cfDNA) to profile cancer-associated mutations has been shown to allow for quantification of disease burden in solid tumors and has also been suggested to enable minimally invasive follow-up of AML patients. In this pilot study we investigated the technical sensitivity and potential prognostic implications of cfDNA-based MRD monitoring in AML after allogeneic stem cell transplantation in comparison to donor chimerism analysis or, respectively, after consolidation chemotherapy. 75 cfDNA samples from 29 patients were analyzed by targeted NGS using a commercially available 10- or 37-gene hotspot panel (VariantPlex Core AML or Core Myeloid panel, ArcherDx). Patients' leukemias exhibited 1-7 mutations as determined by routine diagnostics. Only previously identified mutations were considered for MRD evaluation. cfDNA was isolated in sufficient amounts for NGS from all samples (total yield 24 ng-5.2 µg). The sensitivity of variant detection increased with higher overall read count and higher mutation-specific coverage (variant allele frequency [VAF] range 0.08-100%). At least one previously known mutation was identified in 32/55 samples (58%, VAF 0.08-78.04%) which were taken during hematological complete remission (CR) in both patients after allogeneic stem cell transplantation (aHSCT) and patients after consolidation chemotherapy. In patients after aHSCT (n = 25), at least one previously known mutation was detected in 16/29 cfDNA samples (55.1%, VAF 0.08-6.7%) obtained when donor chimerism was ≥ 90% and in 6/6 samples (100%, VAF: 0.88-63.77%) with reduced donor chimerism. Probability of progression-free survival 17 months after aHSCT in patients with donor chimerism ≥ 90% but mutation-positive cfDNA was 64% compared to 100% in patients with undetectable MRD. In patients after consolidation chemotherapy, cfDNA was positive in all samples taken during CR (n = 4; VAF 0.26-29.84%) and non-CR (n = 4; VAF 8.46-100%). Our results indicate that NGS of cfDNA is suitable for MRD monitoring in AML and offers higher sensitivity for detecting residual leukemic cells than chimerism analysis in patients after aHSCT. Further studies are needed to evaluate clinical relevance of MRD status as determined in cfDNA.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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