IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes
Issued Date
2024-03-01
Resource Type
ISSN
15216616
eISSN
15217035
Scopus ID
2-s2.0-85184613233
Journal Title
Clinical Immunology
Volume
260
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Immunology Vol.260 (2024)
Suggested Citation
Klangkalya N., Stoddard J., Niemela J., Sponaugle J., Greenwell I.B., Reigh E., Kuehn H.S., Kanakry J.A., Rosenzweig S.D., Dimitrova D. IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes. Clinical Immunology Vol.260 (2024). doi:10.1016/j.clim.2024.109922 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/97228
Title
IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes
Corresponding Author(s)
Other Contributor(s)
Abstract
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.