Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The evolution of cellular deficiency in GATA2 mutation

Dickinson, R. E., Milne, P., Jardine, L., Zandi, S., Swierczek, S. I., McGovern, N., Cookson, S., Ferozepurwalla, Z., Langridge, A., Pagan, S., Gennery, A., Heiskanen-Kosma, T., Hamalainen, S., Seppanen, M., Helbert, M., Tholouli, E., Gambineri, E., Reykdal, S., Gottfrethsson, M., Thaventhiran, J. E., Morris, E., Hirschfield, G., Richter, A. G., Jolles, S., Bacon, C. M., Hambleton, S., Haniffa, M., Bryceson, Y., Allen, C., Prchal, J. T., Dick, J. E., Bigley, V. and Collin, M. 2014. The evolution of cellular deficiency in GATA2 mutation. Blood 123 (6) , pp. 863-874. 10.1182/blood-2013-07-517151

Full text not available from this repository.

Abstract

Constitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56bright NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8+ memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: American Society of Hematology
ISSN: 0006-4971
Funders: N/A
Date of Acceptance: 1 December 2013
Last Modified: 07 Jan 2019 13:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/117936

Citation Data

Cited 102 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item