The role of interferon-gamma and its signaling pathway in pediatric hematological disorders.
Animals
Antineoplastic Agents
/ therapeutic use
Benzoates
/ therapeutic use
Child
Drug Discovery
Hematologic Neoplasms
/ drug therapy
Hematopoiesis
/ drug effects
Hematopoietic Stem Cell Transplantation
Humans
Hydrazines
/ therapeutic use
Immunotherapy
Interferon-gamma
/ antagonists & inhibitors
Janus Kinases
/ antagonists & inhibitors
Nitriles
Pyrazoles
/ therapeutic use
Pyrimidines
Signal Transduction
/ drug effects
HLH
aplastic anemia
graft failure
hematologic disorders
interferon-gamma
pediatric
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
27
09
2020
revised:
28
12
2020
accepted:
29
12
2020
pubmed:
24
1
2021
medline:
10
8
2021
entrez:
23
1
2021
Statut:
ppublish
Résumé
Interferon-gamma (IFN-γ) plays a key role in the pathophysiology of hemophagocytic lymphohistiocytosis (HLH), and available evidence also points to a role in other conditions, including aplastic anemia (AA) and graft failure following allogeneic hematopoietic stem cell transplantation. Recently, the therapeutic potential of IFN-γ inhibition has been documented; emapalumab, an anti-IFN-γ monoclonal antibody, has been approved in the United States for treatment of primary HLH that is refractory, recurrent or progressive, or in patients with intolerance to conventional therapy. Moreover, ruxolitinib, an inhibitor of JAK/STAT intracellular signaling, is currently being investigated for treating HLH. In AA, IFN-γ inhibits hematopoiesis by disrupting the interaction between thrombopoietin and its receptor, c-MPL. Eltrombopag, a small-molecule agonist of c-MPL, acts at a different binding site to IFN-γ and is thus able to circumvent its inhibitory effects. Ongoing trials will elucidate the role of IFN-γ neutralization in secondary HLH and future studies could explore this strategy in controlling hyperinflammation due to CAR T cells.
Substances chimiques
Antineoplastic Agents
0
Benzoates
0
Hydrazines
0
Nitriles
0
Pyrazoles
0
Pyrimidines
0
Interferon-gamma
82115-62-6
ruxolitinib
82S8X8XX8H
Janus Kinases
EC 2.7.10.2
eltrombopag
S56D65XJ9G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e28900Informations de copyright
© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
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