Marko Lucijanić1, Vlatko Pejša1,2, Zdravko Mitrović1, Tajana Štoos-Veić3,4, Ana Livun5, Ozren Jakšić1,2, Tamara Vasilj1, Mario Piršić1, Višnja Hariš1, Željko Prka1, Rajko Kušec1,2,4. 1. a Department of Hematology , University Hospital Dubrava , Zagreb , Croatia. 2. b University of Zagreb, School of Medicine , Zagreb , Croatia. 3. c Department of Clinical Cytology and Cytometry , University Hospital Dubrava , Zagreb , Croatia. 4. d University of Osijek, School of Medicine , Croatia. 5. e Clinical Institute of Laboratory Diagnosis, Division of Molecular Diagnosis and Genetics , University Hospital Dubrava , Zagreb , Croatia.
Abstract
OBJECTIVES: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS. METHODS: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene. RESULTS: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P = 0.039) and lower TIBC (P = 0.018). Ferritin was found to be higher for the untransfused mutated patients (P = 0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P = 0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P = 0.004 and P = 0.003, respectively). DISCUSSION: The HFE gene mutations are not more frequent in MDS patients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism. CONCLUSION: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDS patients should be considered for potent iron chelation therapy.
OBJECTIVES: The recent availability of potent oral iron chelators is renewing an interest in the assessment of the possible impact of HFE genetics in MDS. METHODS: Thirty six newly diagnosed patients with MDS were studied for parameters of iron metabolism in addition to C282Y and H63D mutations of the HFE gene. RESULTS: Mutations were present in 11 out of 36 patients (31%), which were not different from our general population and were equally distributed among MDS subtypes. Mutated patients had higher ferritin levels (P = 0.039) and lower TIBC (P = 0.018). Ferritin was found to be higher for the untransfused mutated patients (P = 0.017), but not for transfusion-dependent patients in whom ferritin levels correlated significantly with the number of blood units received (P = 0.04). There was no difference in the number of blood units received between the mutated and wild type patients. A new observation made was that the mutated patients had a lower overall survival in addition to a poorer leukemia free survival (LFS) (P = 0.004 and P = 0.003, respectively). DISCUSSION: The HFE gene mutations are not more frequent in MDSpatients. Iron overload in mutated patients was higher but there was no correlation found using supportive therapy for anemia. The effect of mutations on survival could be mediated by changes in iron metabolism. CONCLUSION: The HFE genotype may predict MDS prognosis and there is a need for further studies. It remains a challenging question if HFE mutated MDSpatients should be considered for potent iron chelation therapy.
Entities:
Keywords:
C282Y; H63D; HFE; Iron metabolism; Myelodysplastic syndrome; Overall Survival
Authors: Mathias Schneeweiss-Gleixner; Georg Greiner; Susanne Herndlhofer; Julia Schellnegger; Maria-Theresa Krauth; Karoline V Gleixner; Friedrich Wimazal; Corinna Steinhauser; Michael Kundi; Renate Thalhammer; Ilse Schwarzinger; Gregor Hoermann; Harald Esterbauer; Manuela Födinger; Peter Valent; Wolfgang R Sperr Journal: Am J Cancer Res Date: 2021-03-01 Impact factor: 6.166