# The effects of the PHF6 gene mutation on myeloid neoplasms. A single-center cohort underpinned by a systematic review of literature

## TL;DR

This study investigates the rare PHF6 gene mutation in myeloid neoplasms and its potential impact on patient prognosis.

## Contribution

The paper provides new evidence on the marginal prognostic role of PHF6 mutations in myeloid neoplasms through a combined cohort and literature review.

## Key findings

- PHF6 mutations were associated with higher mortality in myeloid neoplasms in multivariate analysis.
- The effect of PHF6 mutations was significant in acute myeloid leukemia but not in other myeloid neoplasm subtypes.
- PHF6 mutations showed marginal significance in clinical outcomes but should be interpreted cautiously due to small sample size.

## Abstract

The mutation of the plant homeodomain finger protein 6 gene (PHF6MUT) in patients with myeloid neoplasms (MNs) is rare and appears to play a role in prognosis, though this is still under debate. We conducted a retrospective analysis of a cohort of 313 patients diagnosed with MNs. We also performed a systematic review (SR) of the literature to evaluate the prognostic role of PHF6 gene status in MNs. We identified 15 patients with PHF6MUT. In the multivariate analysis, PHF6MUT was associated with higher mortality compared to PHF6wild − type (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 1.00–1.05; P = 0.075), with no apparent impact from other co-mutations. In the multilevel logistic model by MN subtype, the presence of PHF6MUT (independent of variant allele frequency > 20%) was shown to have a positive coefficient (adverse prognosis) in acute myeloid leukemia; in the remainder of MNs, the effect was not significant. PHF6MUT had a marginal and significant effect compared to PHF6wild − type cases (HR = 1.02; 95% CI, 1.00-1.05; P = 0.039). There were no significant differences in time to blast transformation or time to next treatment depending on PHF6 gene status. According to the results of most studies published to date (SR), PHF6MUT has a prognostic role in MNs; our results are consistent in terms of clinical outcomes, but these marginal effects should be interpreted with caution in the context of existing prognostic models given the limitations of the small sample size.

The online version contains supplementary material available at 10.1007/s00277-026-06766-y.