IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes.

Autor: Klangkalya N; Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, Bethesda, MD, USA; Department of Pediatric, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Stoddard J; Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, Bethesda, MD, USA., Niemela J; Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, Bethesda, MD, USA., Sponaugle J; Center for Immuno-Oncology, National Cancer Institute of the National Institutes of Health, Bethesda, MD, USA., Greenwell IB; Division of Hematology and Medical Oncology, Hollings Cancer Center of the Medical University of South Carolina, Charleston, SC, USA., Reigh E; Section of Allergy and Clinical Immunology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Kuehn HS; Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, Bethesda, MD, USA., Kanakry JA; Center for Immuno-Oncology, National Cancer Institute of the National Institutes of Health, Bethesda, MD, USA., Rosenzweig SD; Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, Bethesda, MD, USA. Electronic address: srosenzweig@cc.nih.gov., Dimitrova D; Center for Immuno-Oncology, National Cancer Institute of the National Institutes of Health, Bethesda, MD, USA. Electronic address: dimana.dimitrova@nih.gov.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2024 Mar; Vol. 260, pp. 109922. Date of Electronic Publication: 2024 Feb 05.
DOI: 10.1016/j.clim.2024.109922
Abstrakt: IKAROS, encoded by IKZF1, is a tumor suppressor and a key hematopoietic transcription factor responsible for lymphoid and myeloid differentiation. IKZF1 mutations result in inborn errors of immunity presenting with increased susceptibility to infections, immune dysregulation, and malignancies. In particular, patients carrying IKZF1 gain-of-function (GOF) mutations mostly exhibit symptoms of immune dysregulation and polyclonal plasma cell proliferation. Herein, we describe seven new IKAROS GOF cases from two unrelated families, presenting with novel infectious, immune dysregulation and hematologic diseases. Two of the patients underwent allogeneic hematopoietic cell transplantation (HCT) due to poorly responsive complications. HCT was well-tolerated achieving full engraftment in both patients receiving reduced intensity, matched unrelated donor grafts, with no severe acute or chronic graft-vs-host-disease, and in remission from their diseases 2.5 and 4 years post-HCT, respectively. These results suggest that HCT is a valid and curative option in patients with IKAROS GOF disease and severe clinical manifestations.
Competing Interests: Declaration of competing interest The authors have no conflicting financial interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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