TP53 mutation status as a transplant-decision modifier in Ph-negative MPN

Current understanding

TP53 mutations are uncommon in chronic-phase Ph-negative MPN but become enriched as disease advances to MF and AP/BP, typically with high clonal burden and a roughly 50/50 split between single-hit and multi-hit configurations. A PRISMA-guided pooled synthesis shows multi-hit TP53 confers a steep OS decrement specifically in chronic-phase disease, while in AP/BP the prognosis is already so poor that multi-hit status adds little further gradient — implying that TP53 (and multi-hit determination) is most actionable as an early-referral trigger in chronic-phase MPN/MF rather than as a bridging-strategy determinant in AP/BP.

Evidence log

• 2026-10-07 — Outcome heterogeneity in CALR-mutated myeloproliferative neoplasms.: Reinforces TP53 as a dominant adverse modifier specifically in CALR-mutated MPN, where co-mutation (not the CALR driver) drives outcome — supporting early-referral triggering on TP53 acquisition regardless of driver mutation. (novelty: 3)
• 2026-09-19 — Clinicopathologic Characteristics of SomaticMutations in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Systematic Review.: cross-connection with mipss70-plus: MIPSS70+ already incorporates high-molecular-risk mutations but does not resolve TP53 single- vs multi-hit; the phase-dependent OS gradient shown here argues for augmenting molecular scoring with TP53 allelic status in chronic-phase MF. (novelty: 3)

Open questions

Related