Iron is a modifier of the phenotypes of JAK2-mutant myeloproliferative neoplasms

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73628206" target="_blank" >RIV/61989592:15110/23:73628206 - isvavai.cz</a>

Result on the web

<a href="https://ashpublications.org/blood/article/141/17/2127/494410/Iron-is-a-modifier-of-the-phenotypes-of-JAK2" target="_blank" >https://ashpublications.org/blood/article/141/17/2127/494410/Iron-is-a-modifier-of-the-phenotypes-of-JAK2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/blood.2022017976" target="_blank" >10.1182/blood.2022017976</a>

Result language

angličtina

Original language name

Iron is a modifier of the phenotypes of JAK2-mutant myeloproliferative neoplasms

Original language description

JAK2-V617F mutation causes myeloproliferative neoplasms (MPNs) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis. At diagnosis, patients with PV already exhibited iron deficiency, whereas patients with ET had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with an N542-E543del mutation in exon 12 (E12). At baseline, on a control diet, all JAK2-mutant mouse models with a PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2V617F mutant mice with an ET-like phenotype had normal iron stores comparable with that of wild-type (WT) mice. On a low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with a PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the premegakaryocyte-erythrocyte progenitors, which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment for patients with PV.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

<a href="/en/project/NV19-07-00412" target="_blank" >NV19-07-00412: Cellular and molecular-genetic characterization of selected hereditary defects of erythropoiesis</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Blood

ISSN

0006-4971

e-ISSN

—

Volume of the periodical

141

Issue of the periodical within the volume

17

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

2127-2140

UT code for WoS article

000991078600001

EID of the result in the Scopus database

2-s2.0-85150764423