Gene Mutations Flag Poor Survival in Advanced Myeloproliferative Neoplasms

Patients with Philadelphia chromosome-negative myeloproliferative neoplasms who progress to the accelerated or blast phase face some of the poorest outcomes in hematology, and a new study now maps which clinical and genetic variables separate longer survivors from shorter ones. Researchers reviewed data from 88 consecutive patients diagnosed and treated at three hospitals between January 2015 and July 2025, comprising 32 patients in accelerated phase and 56 in blast phase. The cohort, reported in Annals of Hematology, had a median follow-up of 16 months, and the team used Cox regression modeling to identify the factors tied to survival.

The analysis confirmed a sharp survival divide between the two disease phases. Patients in accelerated phase lived a median of 32 months, compared with only 12 months for those in blast phase, a difference that reached statistical significance. Treatment responses, however, told a more nuanced story. In accelerated phase, combining hypomethylating agents with ruxolitinib returned 63 percent of patients to chronic phase, while adding venetoclax to a hypomethylating agent achieved 75 percent, a difference the authors reported as not statistically significant. In blast phase, hypomethylating agents plus venetoclax and intensive chemotherapy produced comparable response rates.

Within the accelerated-phase group, older age emerged as the variable significantly associated with poorer survival. The blast-phase picture was more complex. Multivariate analysis identified three adverse clinical predictors: a white blood cell count of 55 × 10⁹ per liter or higher, a prior history of myelofibrosis, and an adverse karyotype. Each of these was significantly linked to shorter survival, underscoring that both disease biology at transformation and the underlying myeloproliferative subtype shape prognosis once blasts appear.

Treatment choice also carried prognostic weight in blast phase. Patients who received either hypomethylating agents combined with venetoclax or intensive chemotherapy survived significantly longer than those who did not, according to the multivariate model. Because the study was a retrospective review of consecutively treated patients rather than a randomized trial, the authors’ conclusion is appropriately measured: these regimens might benefit patients with blast-phase disease, and the association between treatment and survival does not by itself prove causation.

The genetic findings added a molecular layer to the clinical risk model. Among the 70 accelerated- or blast-phase patients with next-generation sequencing data available, mutations in TP53, EZH2, and SF3B1 were each associated with poorer survival. The authors conclude that these mutations predicted poor survival beyond the adverse clinical variables already captured by the model, suggesting that mutational profiling could sharpen risk assessment at transformation. Taken together, the results offer clinicians a framework for evaluating advanced Philadelphia-negative myeloproliferative neoplasms: phase of disease, age, white blood cell count, myelofibrosis history, karyotype, and mutation status together define prognosis, while venetoclax-based combinations and intensive chemotherapy stand out as the approaches associated with longer survival in blast phase.

Subject of Research: Prognostic clinical and genetic variables in accelerated- and blast-phase Philadelphia chromosome-negative myeloproliferative neoplasms

Article Title: Variables associated with outcome in patients with Philadelphia chromosome-negative accelerated- or blast-phase myeloproliferative neoplasms

Article References: Liu, J., Yang, S., Yu, L., Wei, R., Hu, L., Liu, Y., Li, Z., Wang, J., Zhao, S., Ye, F., Sun, Y., Wang, Y., Xu, L., Zhang, X., Huang, X., & Jiang, Q. (2026). Variables associated with outcome in patients with Philadelphia chromosome-negative accelerated- or blast-phase myeloproliferative neoplasms. Annals of Hematology. https://doi.org/10.1007/s00277-026-07326-0

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07326-0

Keywords: myeloproliferative neoplasms, accelerated phase, blast phase, TP53, EZH2, SF3B1, hypomethylating agents, venetoclax, ruxolitinib, intensive chemotherapy, karyotype, survival