Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia
Date
2011
Authors
Hahn, C.
Chong, C.
Carmichael, C.
Wilkins, E.
Brautigan, P.
Li, X.
Babic, M.
Lin, M.
Carmagnac, A.
Lee, Y.
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Advisors
Journal Title
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Type:
Journal article
Citation
Nature Genetics, 2011; 43(10):1012-1019
Statement of Responsibility
Christopher N Hahn, Chan-Eng Chong, Catherine L Carmichael, Ella J Wilkins, Peter J Brautigan, Xiao-Chun Li, Milena Babic, Ming Lin, Amandine Carmagnac, Young K Lee, Chung H Kok, Lucia Gagliardi, Kathryn L Friend, Paul G Ekert, Carolyn M Butcher, Anna L Brown, Ian D Lewis, L Bik To, Andrew E Timms, Jan Storek, Sarah Moore, Meryl Altree, Robert Escher, Peter G Bardy, Graeme K Suthers, Richard J D'Andrea, Marshall S Horwitz & Hamish S Scott
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DOI
Abstract
We report the discovery of GATA2 as a new myelodysplastic syndrome (MDS)-acute myeloid leukemia (AML) predisposition gene. We found the same, previously unidentified heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2 transcription factor gene segregating with the multigenerational transmission of MDS-AML in three families and a GATA2 c.1063_1065delACA (p.Thr355del) mutation at an adjacent codon in a fourth MDS family.
The resulting alterations reside within the second zinc finger of GATA2, which mediates DNA-binding and protein-protein interactions. We show differential effects of the mutations on the transactivation of target genes, cellular differentiation, apoptosis and global gene expression. Identification of such predisposing genes to familial forms of MDS and AML is critical for more effective diagnosis and prognosis, counseling, selection of related bone marrow transplant donors and development of therapies.
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Link to a related website: http://europepmc.org/articles/pmc3184204?pdf=render, Open Access via Unpaywall
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© 2011 Nature America, Inc. All rights reserved.