Prognostic impact of co-occurring FLT3 mutations across molecular subgroups in intensively treated acute myeloid leukemia: insights from real-world genomic data

Yu-Sung Chang^{1

2}, Feng-Ming Tien^{1

2}, Yu-Wen Wang^{1

3}, Chi-Yuan Yao^{1

4}, Xavier Cheng-Hong Tsai¹, Sao-Chih Ni⁵, Min-Yen Lo⁶, Wan-Hsuan Lee^{1

2

7}, Chien-Chin Lin^{1

4}, Yuan-Yeh Kuo⁸, Yen-Ling Peng¹, Mei-Hsuan Tseng⁸, Bor-Sheng Ko^{1

5

8}, Ming Yao^{1

9}, Hwei-Fang Tien^{1

10}, Hsin-An Hou^{11

12

13}, Wen-Chien Chou¹

Affiliations

¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
⁶ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
⁸ Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁹ Division of cellular therapy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan.
¹⁰ Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
¹¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. hsinanhou@ntu.edu.tw.
¹² Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. hsinanhou@ntu.edu.tw.
¹³ Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. hsinanhou@ntu.edu.tw.

PMID: 41491155
PMCID: PMC12770354
DOI: 10.1038/s41408-025-01438-y

Prognostic impact of co-occurring FLT3 mutations across molecular subgroups in intensively treated acute myeloid leukemia: insights from real-world genomic data

Yu-Sung Chang et al. Blood Cancer J. 2026.

. 2026 Jan 6;16(1):3.

doi: 10.1038/s41408-025-01438-y.

Authors

Affiliations

¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
⁶ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan.
⁸ Tai-Chen Cell Therapy Center, National Taiwan University, Taipei, Taiwan.
⁹ Division of cellular therapy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan.
¹⁰ Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
¹¹ Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. hsinanhou@ntu.edu.tw.
¹² Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. hsinanhou@ntu.edu.tw.
¹³ Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. hsinanhou@ntu.edu.tw.

PMID: 41491155
PMCID: PMC12770354
DOI: 10.1038/s41408-025-01438-y

Abstract

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics: This study was approved by the NTUH Research Ethics Committee (approval numbers: 202109078RINB and 202207050RINB), and all participants provided written informed consent in accordance with the Declaration of Helsinki.

Figures

**Fig. 1. *FLT3*^ITD in molecularly defined AML subgroups and prognostic impact of co-occurring *DNMT3A*, *TET2*, *ASXL1* (DTA) mutations in *NPM1*^MUT/ *FLT3*^ITD AML.**
A Multivariable Cox regression forest plot evaluating the effect of *FLT3*^ITD on overall survival (OS) across molecularly defined AML subgroups. Models were adjusted for age, sex, FLT3 inhibitor use, and HSCT. B Kaplan–Meier curves of OS in *NPM1*^MUT/ *FLT3*^ITD AML according to DTA co-mutation status, compared with ELN 2022 adverse-risk AML. C Event-free survival in *NPM1*^MUT/ *FLT3*^ITD AML stratified by DTA co-mutation status, with comparison to the ELN 2022 adverse-risk group. D Relapse-free survival in *NPM1*^MUT/ *FLT3*^ITD AML according to DTA co-mutation status and ELN 2022 adverse-risk classification. TF transcription factor, HSCT hematopoietic stem cell transplantation.

**Fig. 2. Transcriptomic profiling of *FLT3*^ITD versus *FLT3*^WT acute myeloid leukemia (AML).**
A Principal component analysis (PCA) demonstrating distinct clustering of transcriptomic profiles according to *FLT3*^ITD mutation status. B Volcano plot depicting differentially expressed genes (DEGs) between *FLT3*^ITD and *FLT3*^WT AML samples. C Heatmap of normalized gene rexpression values of the top upregulated and downregulated DEGs. D Dot plot showing hallmark pathways significantly enriched in upregulated genes in *FLT3*^ITD AML. E Dot plot showing hallmark pathways significantly enriched in downregulated genes in *FLT3*^ITD AML.

See this image and copyright information in PMC

References

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Prognostic impact of co-occurring FLT3 mutations across molecular subgroups in intensively treated acute myeloid leukemia: insights from real-world genomic data

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Prognostic impact of co-occurring FLT3 mutations across molecular subgroups in intensively treated acute myeloid leukemia: insights from real-world genomic data

Authors

Affiliations

Abstract

Conflict of interest statement

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