Abstract
ABSTRACT
Background
TP53
mutations (
TP53
m) are uncommon in chronic‐phase Ph–negative myeloproliferative neoplasms but become enriched in myelofibrosis (MF) and accelerated/blast phase myeloproliferative (AP/BP‐MPN). Their prevalence, allelic distribution, and phase‐stratified outcomes have not been systematically synthesized.
Methods
A PRISMA‐guided systematic review of EMBASE and PubMed identified cohort studies of adult Ph–negative MPN with molecularly confirmed
TP53
m. Pooled proportions with 95% CI were generated using random‐effects models; survival outcomes were summarized descriptively.
Results
Eleven retrospective cohort studies (
N
= 603) met inclusion criteria.
TP53
m were uncommon overall (3%, 95% CI: 1–13;
I
2
= 97%) but substantially enriched in MF or AP/BP‐MPN cohorts (10%, 95% CI: 4–24;
I
2
= 89%). Among
TP53
m patients, disease distribution included AP/BP‐MPN (33%, 95% CI: 26–41), MF (31%, 95% CI: 15–54), ET (16%, 95% CI: 5–41), and PV (11%, 95% CI: 4–27). Single‐ and multi‐hit
TP53
were present in comparable proportions (52% vs. 48%), with a pooled mean VAF of 37.48% (95% CI: 30.73–44.24;
I
2
= 97%). Unfavorable karyotype was identified in 42%. Median OS was: 37.4–72 months in PV, 44.4–54.6 months in ET, 11.6–24.7 months in MF, and 4.5–6 months in AP/BP‐MPN. In CP‐MPN, multi‐hit
TP53
conferred worse OS (9.5–18.5 months) versus single‐hit disease (38 months to not reached); this distinction was absent in AP/BP‐MPN. Leukemic transformation occurred in 35% (95% CI: 16–60;
I
2
= 93%) across two reporting cohorts, and allo‐HCT was utilized in only 16% (95% CI: 13–19;
I
2
= 12%).
Conclusions
TP53
m Ph–negative MPN are enriched in advanced‐phase disease, carry comparable proportions of single‐hit and multi‐hit allelic configurations with high clonal burden, and demonstrate a clinically important survival gradient. Allelic status is a key prognostic determinant in CP‐MPN but loses significance in AP/BP‐MPN where outcomes are uniformly dismal. Standardized molecular reporting and prospective clinical trials are needed.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission.