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The role of interferon‐gamma and its signaling pathway in pediatric hematological disorders
Author(s) -
Merli Pietro,
Quintarelli Concetta,
Strocchio Luisa,
Locatelli Franco
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28900
Subject(s) - medicine , hemophagocytic lymphohistiocytosis , immunology , thrombopoietin receptor , haematopoiesis , hematopoietic stem cell transplantation , ruxolitinib , aplastic anemia , thrombopoietin , cancer research , transplantation , stem cell , disease , bone marrow , biology , microbiology and biotechnology , myelofibrosis
Abstract 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.