In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 7, No. 69 ( 2022-03-25)
Abstract:
IKZF1 encodes the master transcription factor IKAROS, which has crucial roles at multiple stages of lymphocyte development and hematopoiesis. Genetic variants in IKZF1 have been reported in patients with leukemia and immunodeficiencies. Using whole-exome sequencing in families with clinical presentation of autoimmune, allergic, inflammatory, and lymphoproliferative symptoms, Hoshino et al. identified a heterozygous mutation in IKZF1 at position R183. IKZF1 R183H/C variants functioned as gain-of-function alleles, causing a novel disease entity characterized by eosinophilia, abnormal plasma cell proliferation, and impaired T cell differentiation including increased T helper 2 and low regulatory T cells. Degradation of IKZF1 using lenalidomide rescued some of these defects in in vitro assays, suggesting that lenalidomide may be a promising approach to treat patients with IKZF1 R183H/C variants.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abi7160
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022