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Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells

Lookup NU author(s): Dr Venetia BigleyORCiD, Dr Rachel Dickinson, Professor Matthew CollinORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society of Hematology, 2017.

For re-use rights please refer to the publisher's terms and conditions.


© 2017, American Society of Hematology. All rights reserved. Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor promyelocytic leukemia zinc finger (PLZF), as well as expression of intracellular signaling proteins Fc«Rg, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated manner. Moreover, consistent with an adaptive identity, NK cells from patients with GATA2 mutation displayed altered expression of cytotoxic granule constituents and produced interferon-g upon Fc-receptor engagement but not following combined interleukin-12 (IL-12) and IL-18 stimulation. Canonical, PLZF-expressing NK cells were retained in asymptomatic carriers of GATA2 mutation. Developmentally, GATA-binding protein-2 (GATA-2) was expressed in hematopoietic stem cells, but not in NK-cell progenitors, CD32CD56bright, canonical, or adaptive CD32CD56dim NK cells. Peripheral blood NK cells from individuals with GATA2 mutation proliferated normally in vitro, whereas lineage-negative progenitors displayed impaired NK-cell differentiation. In summary, adaptive NK cells can persist in patients with GATA2 mutation, even after NK-cell progenitors expire. Moreover, our data suggest that adaptive NK cells are more long-lived than canonical, immunoregulatory NK cells.

Publication metadata

Author(s): Schlums H, Jung M, Han H, Theorell J, Bigley V, Chiang SCC, Allan DSJ, Davidson-Moncada JK, Dickinson RE, Holmes TD, Hsu AP, Townsley D, Winkler T, Wang W, Aukrust P, Nordøy I, Calvo KR, Holland SM, Collin M, Dunbar CE, Bryceson YT

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2017

Volume: 129

Issue: 14

Pages: 1927-1939

Print publication date: 06/04/2017

Online publication date: 06/04/2017

Acceptance date: 02/02/2017

Date deposited: 26/01/2018

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2016-08-734236

PubMed id: 28209719


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