JAK2-V617F and interferon-alpha induce megakaryocyte-biased stem cells characterized by decreased long-term functionality
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F21%3A73610669" target="_blank" >RIV/61989592:15110/21:73610669 - isvavai.cz</a>
Result on the web
<a href="https://ashpublications.org/blood/article/137/16/2139/475343/JAK2-V617F-and-interferon-induce-megakaryocyte" target="_blank" >https://ashpublications.org/blood/article/137/16/2139/475343/JAK2-V617F-and-interferon-induce-megakaryocyte</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2020005563" target="_blank" >10.1182/blood.2020005563</a>
Alternative languages
Result language
angličtina
Original language name
JAK2-V617F and interferon-alpha induce megakaryocyte-biased stem cells characterized by decreased long-term functionality
Original language description
We studied a subset of hematopoietic stem cells (HSCs) that are defined by elevated expression of CD41 (CD41(hi)) and showed bias for differentiation toward megakaryocytes (Mks). Mouse models of myeloproliferative neoplasms (MPNs) expressing JAK2-V617F (VF) displayed increased frequencies and percentages of the CD41(hi) vs CD41(lo) HSCs compared with wild-type controls. An increase in CD41(hi) HSCs that correlated with JAK2-V617F mutant allele burden was also found in bone marrow from patients with MPN. CD41(hi) HSCs produced a higher number of Mk-colonies of HSCs in single-cell cultures in vitro, but showed reduced long-term reconstitution potential compared with CD41(lo) HSCs in competitive transplantations in vivo. RNA expression profiling showed an upregulated cell cycle, Myc, and oxidative phosphorylation gene signatures in CD41(hi) HSCs, whereas CD41(lo) HSCs showed higher gene expression of interferon and the JAK/STAT and TNF alpha/NF kappa B signaling pathways. Higher cell cycle activity and elevated levels of reactive oxygen species were confirmed in CD41(hi) HSCs by flow cytometry. Expression of Epcr, a marker for quiescent HSCs inversely correlated with expression of CD41 in mice, but did not show such reciprocal expression pattern in patients with MPN. Treatment with interferon-alpha further increased the frequency and percentage of CD41(hi) HSCs and reduced the number of JAK2-V617F(+) HSCs in mice and patients with MPN. The shift toward the CD41(hi) subset of HSCs by interferon-alpha provides a possible mechanism of how interferon-alpha preferentially targets the JAK2 mutant clone.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/GA17-05988S" target="_blank" >GA17-05988S: Initiation and progression of myeloproliferative disorders – the role of pathological JAK2 activation in the specific context of EPOR</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
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Volume of the periodical
137
Issue of the periodical within the volume
16
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
2139-2151
UT code for WoS article
000646136700008
EID of the result in the Scopus database
2-s2.0-85104668157