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https://hdl.handle.net/2440/68582
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Type: | Journal article |
Title: | Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia |
Author: | Hahn, C. Chong, C. Carmichael, C. Wilkins, E. Brautigan, P. Li, X. Babic, M. Lin, M. Carmagnac, A. Lee, Y. Kok, C. Gagliardi, L. Friend, K. Ekert, P. Butcher, C. Brown, A. Lewis, I. To, L. Timms, A. Storek, J. et al. |
Citation: | Nature Genetics, 2011; 43(10):1012-1019 |
Publisher: | Nature Publishing Group |
Issue Date: | 2011 |
ISSN: | 1061-4036 1546-1718 |
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 |
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. |
Keywords: | COS Cells Animals Humans Myelodysplastic Syndromes Genetic Predisposition to Disease DNA, Complementary Chromosome Mapping Pedigree Cell Differentiation Cell Proliferation Amino Acid Sequence Haplotypes Quantitative Trait, Heritable Mutation Polymorphism, Single Nucleotide Plasmids Molecular Sequence Data Female Male GATA2 Transcription Factor Leukemia, Myeloid, Acute HEK293 Cells Chlorocebus aethiops |
Rights: | © 2011 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/ng.913 |
Published version: | http://dx.doi.org/10.1038/ng.913 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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