Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults

Essential thrombocythaemia (ET) in adolescents and young adults (AYA, 15-39 years) is a distinct entity with an incompletely defined prognosis. In this multicentre retrospective study, 1728 ET patients from 29 centres across China were stratified into AYA (n = 328) and non-AYA (≥40 years, n = 1400) cohorts. We compared their clinical profiles, genomic landscapes, long-term outcomes and risk factors for progression to post-ET myelofibrosis (MF). AYA patients had fewer cardiovascular risks and lower thrombosis rates, but higher rates of extreme thrombocytosis. Molecularly, AYA patients were enriched for calreticulin (CALR) mutations, whereas Janus kinase 2 (JAK2) predominated in older patients. The burden of non-driver mutations (tet methylcytosine dioxygenase 2 [TET2], DNA methyltransferase 3A [DNMT3A], ASXL transcriptional regulator 1 [ASXL1], SH2‑B adaptor protein 3 [SH2B3]) was lower in AYA patients. Consequently, AYA patients achieved superior long-term outcomes across all key survival endpoints, including overall, myelofibrosis-free and leukaemia-free survival. Analysis of post-ET MF progression risks identified age-specific patterns: CALR mutations are enriched in younger patients and show an age-specific association with MF progression. AYA-ET constitutes a unique clinicomolecular subtype with a favourable prognosis, supporting age-stratified management. The enrichment of CALR mutations and their specific link to MF progression in young patients underscore the urgent need for targeted therapies against CALR-mutant clones.

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Journal
British Journal of Haematology
Published
2026-09-04
DOI
https://doi.org/10.1111/bjh.70818
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
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article
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article

Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults

Jie Jin, Jian Huang, Guoli Yao, Xianghua Lang et al.
British Journal of Haematology
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults

Jie Jin, Jian Huang, Guoli Yao, Xianghua Lang, Bingbing Wen, Weiying Feng, Muqing He, Hongyan Tong, Meiwei Hu, Huyi Lei, Qinli Tang, Xiujie Zhou, Jia Li, Ying Lu, Mei Zhou, Huiqi Zhang, Zhaohao Huang, Xiudi Yang, Yanping Shao, Dan Cao, Lifeng Wang, Xiaojing Bao, Gang Zhang, Yu Chen, Yanxia Han, Hangping Ge, Hui Zhou, Lihong Cao, Binbin Lai, Xiao Yan, Honglan Qian, Feng Zhu, Sai Chen, Li Zhang, Li Huang, Yongming Xia
article en

Abstract

Essential thrombocythaemia (ET) in adolescents and young adults (AYA, 15-39 years) is a distinct entity with an incompletely defined prognosis. In this multicentre retrospective study, 1728 ET patients from 29 centres across China were stratified into AYA (n = 328) and non-AYA (≥40 years, n = 1400) cohorts. We compared their clinical profiles, genomic landscapes, long-term outcomes and risk factors for progression to post-ET myelofibrosis (MF). AYA patients had fewer cardiovascular risks and lower thrombosis rates, but higher rates of extreme thrombocytosis. Molecularly, AYA patients were enriched for calreticulin (CALR) mutations, whereas Janus kinase 2 (JAK2) predominated in older patients. The burden of non-driver mutations (tet methylcytosine dioxygenase 2 [TET2], DNA methyltransferase 3A [DNMT3A], ASXL transcriptional regulator 1 [ASXL1], SH2‑B adaptor protein 3 [SH2B3]) was lower in AYA patients. Consequently, AYA patients achieved superior long-term outcomes across all key survival endpoints, including overall, myelofibrosis-free and leukaemia-free survival. Analysis of post-ET MF progression risks identified age-specific patterns: CALR mutations are enriched in younger patients and show an age-specific association with MF progression. AYA-ET constitutes a unique clinicomolecular subtype with a favourable prognosis, supporting age-stratified management. The enrichment of CALR mutations and their specific link to MF progression in young patients underscore the urgent need for targeted therapies against CALR-mutant clones.

British Journal of Haematology
Zhejiang Chinese Medical University (CN), Wenzhou Medical University (CN), First Affiliated Hospital of Wenzhou Medical University (CN), Jiaxing University (CN), Affiliated Hospital of Hangzhou Normal University (CN), Huzhou Central Hospital (CN), Lishui Central Hospital (CN), Jinhua Academy of Agricultural Sciences (CN), Wuhu No 1 People's Hospital (CN), Zhoushan Hospital (CN), Zhejiang Shuren University (CN), Taizhou Central Hospital (CN), First Hospital of Jiaxing (CN), Third People's Hospital of Huzhou (CN), First People's Hospital of Nanning (CN), Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine (CN), Zigong First People's Hospital (CN), Ningbo University Affiliated Hospital (CN), Xiangshan County First People's Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Zhejiang Taizhou Hospital (CN), Shaoxing People's Hospital (CN), Jinhua Central Hospital (CN), Yuxian People's Hospital (CN), Ningbo First Hospital (CN), First Affiliated Hospital Zhejiang University (CN)
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Openalex Percentile: Top 10%
Myeloproliferative Neoplasms: Diagnosis and Treatment
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