Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults.
This multicentre retrospective cohort reports that adolescents and young adults with essential thrombocythaemia have distinct clinical and mutational profiles, better long-term outcomes than older patients, and an age-specific association between CALR mutations and progression to post-ET myelofibrosis.
Open original publication →What the AI sees
This multicentre retrospective cohort reports that adolescents and young adults with essential thrombocythaemia have distinct clinical and mutational profiles, better long-term outcomes than older patients, and an age-specific association between CALR mutations and progression to post-ET myelofibrosis.
Research significance
The evidence supports CALR status and age as candidate factors for risk stratification in AYA essential thrombocythaemia; it is an inference—not tested here—that selectively targeting CALR-mutant clones could prevent or delay myelofibrosis progression.
Source 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.