Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/72032
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Type: Journal article
Title: Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature
Author: Kazenwadel, J.
Secker, G.
Liu, Y.
Rosenfeld, J.
Wildin, R.
Cuellar-Rodriguez, J.
Hsu, A.
Dyack, S.
Fernandez, C.
Chong, C.
Babic, M.
Bardy, P.
Shimamura, A.
Zhang, M.
Walsh, T.
Holland, S.
Hickstein, D.
Horwitz, M.
Hahn, C.
Scott, H.
et al.
Citation: Blood, 2012; 119(5):1283-1291
Publisher: Amer Soc Hematology
Issue Date: 2012
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Jan Kazenwadel... Chan-Eng Chong... Christopher N. Hahn... Hamish S. Scott... Natasha L. Harvey... et al.
Abstract: Recent work has established that heterozygous germline GATA2 mutations predispose carriers to familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), “MonoMAC” syndrome, and DCML deficiency. Here, we describe a previously unreported MDS family carrying a missense GATA2 mutation (p.Thr354Met), one patient with MDS/AML carrying a frameshift GATA2 mutation (p.Leu332Thrfs*53), another with MDSharboring a GATA2 splice site mutation, and 3 patients exhibiting MDS or MDS/AML who have large deletions encompassing the GATA2 locus. Intriguingly, 2 MDS/AML or “MonoMAC” syndrome patients with GATA2 deletions and one with a frameshift mutation also have primary lymphedema. Primary lymphedema occurs as a result of aberrations in the development and/or function of lymphatic vessels, spurring us to investigate whether GATA2 plays a role in the lymphatic vasculature. We demonstrate here that GATA2 protein is present at high levels in lymphatic vessel valves and that GATA2 controls the expression of genes important for programming lymphatic valve development. Our data expand the phenotypes associated with germline GATA2 mutations to include predisposition to primary lymphedema and suggest that complete haploinsufficiency or loss of function of GATA2, rather than missense mutations, is the key predisposing factor for lymphedema onset. Moreover, we reveal a crucial role for GATA2 in lymphatic vascular development.
Keywords: Monocytes; Cells, Cultured; Lymphatic Vessels; Animals; Mice, Inbred C57BL; Mice, Transgenic; Humans; Mice; Myelodysplastic Syndromes; Lymphedema; Syndrome; Lymphangiogenesis; Germ-Line Mutation; Adolescent; Adult; Child; Infant, Newborn; Female; Male; GATA2 Transcription Factor; Leukemia, Myeloid, Acute; Young Adult
Rights: © 2012 by The American Society of Hematology
RMID: 0020116743
DOI: 10.1182/blood-2011-08-374363
Appears in Collections:Medicine publications

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