CALR-mutated MPN outcome heterogeneity from HMR co-mutations

Current understanding

In CALR-mutated MPN, prognosis is driven not by the CALR driver itself but by acquired high-molecular-risk co-mutations — particularly TP53, KRAS, and RUNX1 — which independently worsen leukemia-free and overall survival. This observational signal argues for serial molecular profiling across the disease course rather than reliance on baseline driver status, and for lowering the threshold to refer CALR-mutated patients to transplant once an HMR co-mutation emerges, even if MIPSS70-plus v2.0 does not yet reclassify them.

Evidence log

• 2026-10-07 — Outcome heterogeneity in CALR-mutated myeloproliferative neoplasms.: cross-connection with tp53-mutations-mpn-transplant-risk: CALR-mutated MPN is a specific context where TP53 acquisition should trigger early transplant referral, since the CALR driver itself is prognostically neutral. (novelty: 3)

Open questions

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