Study identifies 4 clinically distinct myelofibrosis subtypes that have different survival prognoses

A study identified four biologically and clinically distinct myelofibrosis (MF) subtypes—MF-immune, MF-erythroid, MF-myeloid, and MF-MEP—and each conferred different survival outcomes.

Andy Zeng, MD, PhD, of Princess Margaret Cancer Centre in Toronto, Canada, and colleagues presented the findings at the 2026 EHA Congress.

The researchers sought to assess non-genetic factors to explain the heterogeneity of the clinical presentation and outcomes associated with MF. They assessed peripheral blood from 358 patients in a discovery cohort and 168 in a validation cohort.

They established four transcriptionally and clinically distinct subtypes:

1. MF-Immune, presenting in 116 patients, conferring the lowest disease burden
2. MF-Erythroid, presenting in 72 patients
3. MF-Myeloid, presenting in 88 patients
4. MF-MEP, presenting in 82 patients, conferring the highest disease burden

These subtypes were independent of canonical driver mutational status (P=0.89), and each differed significantly in blood counts, cytopenias, peripheral blast percentage, fibrosis grade, and splenomegaly (P<0.001 for all).

Five-year survival was 85% for MF-Immune, 58% for MF-Erythroid, 38% for MF-Myeloid, and 26% for MF-MEP, and survival was confirmed after adjusting for Dynamic International Prognostic Scoring System and Mutation-Enhanced International Prognostic Score System 70 risk scores.

The five-year risk of transformation to acute myeloid leukemia (AML) was 20% with MF-MEP, 19% with MF-Myeloid, 5% with MF-Erythroid, and 5% with MF-Immune.

In a cohort of 20 paired MF to secondary AML (sAML) samples, the sAML retained transcriptional features of the antecedent MF subtype, “suggesting that disease history in chronic phase shapes biology after AML transformation,” according to the authors.

Reference

Zeng A, Medeiros J, Bhagirath A, et al. Transcriptional subtypes of myelofibrosis are independent of driver mutations and capture distinct biology, outcomes, and disease trajectories. Abstract #6628. Presented at the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden.