Elevated erythroferrone distinguishes erythrocytosis with
inherited defects in oxygen-sensing pathway from primary
familial and congenital polycythaemia

J 2023

Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia

SOCHORCOVA, Lucie, Katarina HLUSICKOVA KAPRALOVA, Jana FIALOVÁ KUČEROVÁ, Dagmar POSPISILOVA, Daniela PROCHAZKOVA et. al.

Basic information

Original name

Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia

Authors

SOCHORCOVA, Lucie (203 Czech Republic), Katarina HLUSICKOVA KAPRALOVA (203 Czech Republic), Jana FIALOVÁ KUČEROVÁ (203 Czech Republic, belonging to the institution), Dagmar POSPISILOVA (203 Czech Republic), Daniela PROCHAZKOVA (203 Czech Republic), Ondrej JAHODA (203 Czech Republic), Simona KUREKOVA (203 Czech Republic), Barbora KRALOVA (203 Czech Republic), Martina DIVOKA (203 Czech Republic), Jana NAVRATILOVA (203 Czech Republic), Jirina MANAKOVA (203 Czech Republic), Eva KRIEGOVA (203 Czech Republic), Karel INDRAK (203 Czech Republic), Edgar FABER (203 Czech Republic), Vladimir DIVOKY (203 Czech Republic) and Monika HORVATHOVA (203 Czech Republic)

Edition

British journal of haematology, Hoboken, Wiley-Blackwell, 2023, 0007-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.500 in 2022

RIV identification code

RIV/00216224:14110/23:00133658

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1111/bjh.18891

UT WoS

000996117400001

Keywords in English

EPOR; erythrocytosis; erythroferrone; hepcidin; VHL

Abstract

V originále

Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia-inducible factor 2 alpha (HIF2A) or Von Hippel-Lindau (VHL) genes were detected in nine patients, including a novel p.A421Cfs*4 EPOR and a homozygous intronic c.340+770T>C VHL mutation. The association and possible cooperation of five identified missense germline EPOR or Janus kinase 2 (JAK2) variants with other genetic/non-genetic factors in erythrocytosis manifestation may involve variants of Piezo-type mechanosensitive ion channel component 1 (PIEZO1) or Ten-eleven translocation 2 (TET2), but this requires further research. In two families, hepcidin levels appeared to prevent or promote phenotypic expression of the disease. No major contribution of heterozygous haemochromatosis gene (HFE) mutations to the erythrocytic phenotype or hepcidin levels was observed in our cohort. VHL- and HIF2A-mutant erythrocytosis showed increased erythroferrone and suppressed hepcidin, whereas no overproduction of erythroferrone was detected in other patients regardless of molecular defect, age or therapy. Understanding the interplay between iron metabolism and erythropoiesis in different subgroups of congenital erythrocytosis may improve current treatment options.

Citovat

SOCHORCOVA, Lucie, Katarina HLUSICKOVA KAPRALOVA, Jana FIALOVÁ KUČEROVÁ, Dagmar POSPISILOVA, Daniela PROCHAZKOVA, Ondrej JAHODA, Simona KUREKOVA, Barbora KRALOVA, Martina DIVOKA, Jana NAVRATILOVA, Jirina MANAKOVA, Eva KRIEGOVA, Karel INDRAK, Edgar FABER, Vladimir DIVOKY and Monika HORVATHOVA. Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia. British journal of haematology. Hoboken: Wiley-Blackwell, 2023, vol. 202, No 3, p. 674-685. ISSN 0007-1048. Available from: https://dx.doi.org/10.1111/bjh.18891.

@article{2379083,
   author = {Sochorcova, Lucie and Hlusickova Kapralova, Katarina and Fialová Kučerová, Jana and Pospisilova, Dagmar and Prochazkova, Daniela and Jahoda, Ondrej and Kurekova, Simona and Kralova, Barbora and Divoka, Martina and Navratilova, Jana and Manakova, Jirina and Kriegova, Eva and Indrak, Karel and Faber, Edgar and Divoky, Vladimir and Horvathova, Monika},
   article_location = {Hoboken},
   article_number = {3},
   doi = {http://dx.doi.org/10.1111/bjh.18891},
   keywords = {EPOR; erythrocytosis; erythroferrone; hepcidin; VHL},
   language = {eng},
   issn = {0007-1048},
   journal = {British journal of haematology},
   title = {Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia},
   url = {https://onlinelibrary.wiley.com/doi/10.1111/bjh.18891},
   volume = {202},
   year = {2023}
}

TY  - JOUR
ID  - 2379083
AU  - Sochorcova, Lucie - Hlusickova Kapralova, Katarina - Fialová Kučerová, Jana - Pospisilova, Dagmar - Prochazkova, Daniela - Jahoda, Ondrej - Kurekova, Simona - Kralova, Barbora - Divoka, Martina - Navratilova, Jana - Manakova, Jirina - Kriegova, Eva - Indrak, Karel - Faber, Edgar - Divoky, Vladimir - Horvathova, Monika
PY  - 2023
TI  - Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia
JF  - British journal of haematology
VL  - 202
IS  - 3
SP  - 674-685
EP  - 674-685
PB  - Wiley-Blackwell
SN  - 00071048
KW  - EPOR
KW  - erythrocytosis
KW  - erythroferrone
KW  - hepcidin
KW  - VHL
UR  - https://onlinelibrary.wiley.com/doi/10.1111/bjh.18891
N2  - Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia-inducible factor 2 alpha (HIF2A) or Von Hippel-Lindau (VHL) genes were detected in nine patients, including a novel p.A421Cfs*4 EPOR and a homozygous intronic c.340+770T>C VHL mutation. The association and possible cooperation of five identified missense germline EPOR or Janus kinase 2 (JAK2) variants with other genetic/non-genetic factors in erythrocytosis manifestation may involve variants of Piezo-type mechanosensitive ion channel component 1 (PIEZO1) or Ten-eleven translocation 2 (TET2), but this requires further research. In two families, hepcidin levels appeared to prevent or promote phenotypic expression of the disease. No major contribution of heterozygous haemochromatosis gene (HFE) mutations to the erythrocytic phenotype or hepcidin levels was observed in our cohort. VHL- and HIF2A-mutant erythrocytosis showed increased erythroferrone and suppressed hepcidin, whereas no overproduction of erythroferrone was detected in other patients regardless of molecular defect, age or therapy. Understanding the interplay between iron metabolism and erythropoiesis in different subgroups of congenital erythrocytosis may improve current treatment options.
ER  -

SOCHORCOVA, Lucie, Katarina HLUSICKOVA KAPRALOVA, Jana FIALOVÁ KUČEROVÁ, Dagmar POSPISILOVA, Daniela PROCHAZKOVA, Ondrej JAHODA, Simona KUREKOVA, Barbora KRALOVA, Martina DIVOKA, Jana NAVRATILOVA, Jirina MANAKOVA, Eva KRIEGOVA, Karel INDRAK, Edgar FABER, Vladimir DIVOKY and Monika HORVATHOVA. Elevated erythroferrone distinguishes erythrocytosis with inherited defects in oxygen-sensing pathway from primary familial and congenital polycythaemia. \textit{British journal of haematology}. Hoboken: Wiley-Blackwell, 2023, vol.~202, No~3, p.~674-685. ISSN~0007-1048. Available from: https://dx.doi.org/10.1111/bjh.18891.

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