HFE mutation status may affect outcomes among patients with a myelodysplastic syndrome (MDS), though further research is necessary to determine whether any links are statistically significant, according to research published in the American Journal of Cancer Research.

MDS, which represents a set of hematologic cancers, is characterized by the presence of abnormal myeloid precursor cells and bone marrow failure with peripheral blood cytopenia, and carries a highly variable prognosis because of its varying morphological features. While the Revised International Prognostic Scoring System (IPSS-R) is widely used to stratify patients by risk category, novel features of interest are frequently introduced as potential prognostic biomarkers in the MDS setting.

Among these biomarkers is HFE, which is known to be involved in iron uptake and metabolism. As patients with MDS are more likely than healthy controls to have chronic iron overload, which is determined by serum ferritin levels, HFE mutation rates in this patient population may prove to be prognostically and clinically significant.

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For this study, researchers evaluated the rates and significance of HFE variants in a population of patients with MDS in an effort to determine any relationship between these mutations and serum ferritin levels or clinical outcomes.

Overall, data from 167 patients with MDS and 494 healthy volunteers were included in this study. One of 3 HFE mutations of interest (H63D, C282Y, and S65C) was noted in 38.9% (65) of patients with MDS and in 33.2% (164) of controls. Median serum ferritin levels at MDS diagnosis were numerically, but not significantly, higher among patients with an HFE mutation vs patients without an HFE mutation (P =.62).

Progression-free survival and overall survival also showed no significant difference between the group of patients with a mutation vs those without (P =.089 and P =.44, respectively).

“Although clear differences were seen, the significance level was not reached in all these comparisons which is most probably due to the relatively small number of cases examined in each cohort,” the authors wrote. “Therefore, more studies with more patients are required to finally elucidate the role of HFE-variants in MDS.”

Disclosure: Several study authors declared affiliations with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.


Schneeweiss-Gleixner M, Greiner G, Herndlhofer S, et al. Impact of HFE gene variants on iron overload, overall survival and leukemia-free survival in myelodysplastic syndromes. Am J Cancer Res. 2021;11(3):955-967.