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

Authors

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

Published in

British journal of haematology. Sep 04, 2026. Epub Sep 04, 2026.

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.

PMID:
42698068
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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