Impact of HFE gene variants on iron overload, overall survival and leukemia-free survival in myelodysplastic syndromes

被引：1

作者：

Schneeweiss-Gleixner, Mathias ^{[1
,2
,3
]}

Greiner, Georg ^{[2
,4
,5
]}

Herndlhofer, Susanne ^{[1
]}

Schellnegger, Julia ^{[4
]}

Krauth, Maria-Theresa ^{[1
,2
]}

Gleixner, Karoline, V ^{[1
,2
]}

Wimazal, Friedrich ^{[1
,6
]}

Steinhauser, Corinna ^{[7
]}

Kundi, Michael ^{[8
]}

Thalhammer, Renate ^{[4
]}

Schwarzinger, Ilse ^{[4
]}

Hoermann, Gregor ^{[2
,4
,9
]}

Esterbauer, Harald ^{[4
]}

Fodinger, Manuela ^{[10
,11
]}

Valent, Peter ^{[1
,2
]}

Sperr, Wolfgang R. ^{[1
,2
]}

机构：

[1] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Med 1, A-1090 Vienna, Austria

[2] Med Univ Vienna, Ludwig Boltzmann Inst Hematol & Oncol, A-1090 Vienna, Austria

[3] Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Med 3, A-1090 Vienna, Austria

[4] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria

[5] Med Diagnost Labs, Ihr Lab, A-1220 Vienna, Austria

[6] Med Univ Vienna, Dept Obstet & Gynecol, A-1090 Vienna, Austria

[7] Med Univ Vienna, Div Nephrol, Dept Med 3, A-1090 Vienna, Austria

[8] Med Univ Vienna, Inst Environm Hlth, A-1090 Vienna, Austria

[9] MLL Munich Leukemia Lab, Munich, Germany

[10] Clin Favoriten, Inst Lab Diagnost, A-1100 Vienna, Austria

[11] Sigmund Freud Private Univ, Med Fac, A-1020 Vienna, Austria

来源：

AMERICAN JOURNAL OF CANCER RESEARCH | 2021年 / 11卷 / 03期

基金：

奥地利科学基金会;

关键词：

MDS; ferritin; iron overload; HFE gene variants; iron chelation; NGS; PROGNOSTIC SCORING SYSTEM; TRANSFUSION-DEPENDENT PATIENTS; RISK-ASSESSMENT; HEREDITARY HEMOCHROMATOSIS; PREDICTING SURVIVAL; COMORBIDITY INDEX; CLASSIFICATION; MUTATIONS; DIAGNOSIS; PROPOSALS;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Although iron overload is a clinical challenge, little is known about the clinical impact of HFE-variants in myelodysplastic syndromes (MDS) to date. We analyzed the HFE status in 167 MDS patients and 494 healthy controls. One or more of the 3 HFE-variants (H63D, C282Y, S65C) were found in 65/167 (38.9%) MDS patients and in 164/494 (33.2%) controls. At diagnosis, the median serum ferritin levels were higher in MDS patients with HFE-variants (409 mu g/L; range: 23-7415) compared to those without HFE-variants (346.5 mu g/L; range: 10-5450) (P=0.62). Moreover, 'HFE-mutated' patients had a slightly faster increase in serum ferritin in follow up examinations. The percentage of patients with HFE-variants was higher in refractory anemia (RA) (22/53=41.5%) or RA with ring sideroblasts (RARS) (17/39=43.6%) compared to RA with excess of blasts (RAEB) (16/46=34.8%) or RAEB in transformation (RAEB-T) (5/17=29.4%). Differences were also detectable when comparing low- and high-risk MDS variants defined by the World Health Organization classification. There was no significant correlation between HFE-variants and MDS-related somatic mutations. Progression-free survival was substantially longer in patients with HFE-variants compared to those without HFE-variants H63D and C282Y (P=0.089). Together, the HFE-variants H63D and C282Y are frequently detected in Austrian MDS patients. These patients have substantially higher ferritin levels at diagnosis, accumulate iron slightly faster and have a better progression-free survival than non-mutated patients.

引用

页码：955 / +

页数：17

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[1] The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia [J].