The comprehensive landscape of <i>TTMV::RARA</i> fusion-driven acute myeloid leukemia: from viral integration mechanisms to clinical outcomes
Acute myeloid leukemia (AML) with TTMV::RARA fusion represents a novel subtype driven by torque teno mini virus (TTMV) integration into retinoic acid receptor alpha (RARA) locus, while current understanding of its molecular features and clinical presentation relies predominantly on isolated case observations. Here, we characterize a large and independent cohort (n=25) through integrative analysis of clinical-omics data, uncovering unique features that distinguish it from classic acute promyelocytic leukemia (APL) and other AML subtypes. Our findings reveal that TTMV integrates exclusively within intron 2 of the RARA gene via microhomology-mediated end joining (MMEJ), forming functional TTMV::RARA transcripts. Clinically, patients harboring this fusion were predominantly pediatric (72.
Authors
- Hongjuan Xue
- Xianjing Wang (ORCID: https://orcid.org/0000-0002-0455-3978)
- Feng Wang
- Yangyang Xie (ORCID: https://orcid.org/0009-0006-1606-3585)
- Suning Chen (ORCID: https://orcid.org/0000-0001-6294-972X)
- Bei Yang
- Haibo Yu (ORCID: https://orcid.org/0000-0002-1744-990X)
- Jinyan Huang (ORCID: https://orcid.org/0000-0003-1641-6580)
- Wei Gao (ORCID: https://orcid.org/0000-0001-7836-2851)
- Shu Sun
- Hong-Hu Zhu
- Wu Yin (ORCID: https://orcid.org/0000-0002-5041-0134)
- Haiyan Wang (ORCID: https://orcid.org/0000-0002-5204-967X)
- Lian Li (ORCID: https://orcid.org/0000-0003-4700-1134)
- Na Li (ORCID: https://orcid.org/0000-0002-3920-513X)
- Jiayu Wang (ORCID: https://orcid.org/0000-0003-0470-0322)
- Li Chen (ORCID: https://orcid.org/0000-0001-9372-5606)
- Jianwei Wang (ORCID: https://orcid.org/0000-0002-1116-4559)
- Kun Chen (ORCID: https://orcid.org/0000-0001-7827-1968)
- Huili Wang (ORCID: https://orcid.org/0000-0002-0984-2963)
- Zhanrui Cheng
- Leping Zhang (ORCID: https://orcid.org/0000-0001-8171-6243)
- Jian Xiao (ORCID: https://orcid.org/0009-0004-5291-1655)
- Lijun Wen (ORCID: https://orcid.org/0000-0002-2508-6168)
- Yongjing Liu (ORCID: https://orcid.org/0000-0001-6746-3913)
- Qingyu Xu (ORCID: https://orcid.org/0000-0003-2281-4454)
- Kankan Wang (ORCID: https://orcid.org/0000-0001-7198-2134)
- Shuhong Shen
- Huan-You Wang
- Jiacheng Lou
Institutions
- Hebei Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Capital Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Beijing Chao-Yang Hospital, Capital Medical University (CN)
- Ruijin Hospital (CN)
- University of California San Diego (US)
- Soochow University (CN)
- Shanghai Children's Medical Center (CN)
- Xingtai People's Hospital (CN)
- Peking University People's Hospital (CN)
- Third Affiliated Hospital of Zhengzhou University (CN)
- Shanghai Institute of Hematology (CN)
- Zhengzhou People's Hospital (CN)
- Yichang Central People's Hospital (CN)
- Zigong First People's Hospital (CN)
- First Affiliated Hospital of Soochow University (CN)
- First Affiliated Hospital Zhejiang University (CN)
Publication Details
- Journal
- Haematologica
- Published
- 2025-11-13
- DOI
- https://doi.org/10.3324/haematol.2025.288721
- Primary Topic
- Retinoids in leukemia and cellular processes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Beijing Postdoctoral Science Foundation
- Cambridge Institute for Medical Research, University of Cambridge