학술논문
Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes.
Document Type
Academic Journal
Author
Kim N; Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Hahn S; Department of Pediatric Hematology-Oncology, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.; Choi YJ; Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Cho H; Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Chung H; Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Jang JE; Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Lyu CJ; Department of Pediatric Hematology-Oncology, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.; Lee ST; Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Dxome Co. Ltd, Seongnam-si, Gyeonggi-do, Korea.; Choi JR; Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.; Dxome Co. Ltd, Seongnam-si, Gyeonggi-do, Korea.; Cheong JW; Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea. JWCHEONG70@yuhs.ac.; Shin S; Department of Laboratory Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea. saeam0304@yuhs.ac.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 101139795 Publication Model: Electronic Cited Medium: Print ISSN: 1475-2867 (Print) Linking ISSN: 14752867 NLM ISO Abbreviation: Cancer Cell Int Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1475-2867
Abstract
Introduction: Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by uncontrolled proliferation of myeloid precursor cells within bone marrow. Despite advances in understanding of its molecular underpinnings, AML remains a therapeutic challenge due to its high relapse rate and clonal evolution.
Methods: In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented.
Results: Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse.
Conclusions: Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.
(© 2024. The Author(s).)
Methods: In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented.
Results: Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse.
Conclusions: Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.
(© 2024. The Author(s).)