Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia

We report the discovery of the GATA2 gene as a new myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) predisposition gene. We found the same, novel heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2 transcription factor gene segregating with the multigenerational transmi...

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Detalles Bibliográficos
Autores principales: Hahn, Christopher N., Chong, Chan-Eng, Carmichael, Catherine L., Wilkins, Ella J., Brautigan, Peter J., Li, Xiao-Chun, Babic, Milena, Lin, Ming, Carmagnac, Amandine, Lee, Young K., Kok, Chung H., Gagliardi, Lucia, Friend, Kathryn L., Ekert, Paul G., Butcher, Carolyn M., Brown, Anna L., Lewis, Ian D., To, L. Bik, Timms, Andrew E., Storek, Jan, Moore, Sarah, Altree, Meryl, Escher, Robert, Bardy, Peter G., Suthers, Graeme K., D’Andrea, Richard J., Horwitz, Marshall S., Scott, Hamish S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184204/
https://www.ncbi.nlm.nih.gov/pubmed/21892162
http://dx.doi.org/10.1038/ng.913
Descripción
Sumario:We report the discovery of the GATA2 gene as a new myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) predisposition gene. We found the same, novel 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/AML family. The mutations reside within the second zinc finger of GATA2 which mediates DNA-binding and protein-protein interactions. We show differential effects of the mutants on 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, counselling, selection of related bone marrow transplant donors, and development of therapies.

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