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Authors
Dickinson, Rachel EMilne, Paul
Jardine, Laura
Zandi, Sasan
Swierczek, Sabina I
McGovern, Naomi
Cookson, Sharon
Ferozepurwalla, Zaveyna
Langridge, Alexander
Pagan, Sarah
Gennery, Andrew
Heiskanen-Kosma, Tarja
Hämäläinen, Sari
Seppänen, Mikko
Helbert, Matthew
Tholouli, Eleni
Gambineri, Eleonora
Reykdal, Sigrún
Gottfreðsson, Magnús
Thaventhiran, James E
Morris, Emma
Hirschfield, Gideon
Richter, Alex G
Jolles, Stephen
Bacon, Chris M
Hambleton, Sophie
Haniffa, Muzlifah
Bryceson, Yenan
Allen, Carl
Prchal, Josef T
Dick, John E
Bigley, Venetia
Collin, Matthew
Issue Date
2014-02-06
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Blood 2014, 123 (6):863-74Abstract
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, CD56(bright) 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.Description
To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAdditional Links
http://dx.doi.org/10.1182/blood-2013-07-517151http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916878/
http://www.bloodjournal.org/content/bloodjournal/123/6/863.full.pdf
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Archived with thanks to Bloodae974a485f413a2113503eed53cd6c53
10.1182/blood-2013-07-517151
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