Cargando…
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2011
|
| Materias: | |
| 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 |
| _version_ | 1782213076709277696 |
|---|---|
| author | 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. |
| author_facet | 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. |
| author_sort | Hahn, Christopher N. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-3184204 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2011 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-31842042012-04-01 Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia 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. Nat Genet Article 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. 2011-09-04 /pmc/articles/PMC3184204/ /pubmed/21892162 http://dx.doi.org/10.1038/ng.913 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article 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. Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title | Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title_full | Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title_fullStr | Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title_full_unstemmed | Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title_short | Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia |
| title_sort | heritable gata2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia |
| topic | Article |
| url | 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 |
| work_keys_str_mv | AT hahnchristophern heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT chongchaneng heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT carmichaelcatherinel heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT wilkinsellaj heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT brautiganpeterj heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT lixiaochun heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT babicmilena heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT linming heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT carmagnacamandine heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT leeyoungk heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT kokchungh heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT gagliardilucia heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT friendkathrynl heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT ekertpaulg heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT butchercarolynm heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT brownannal heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT lewisiand heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT tolbik heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT timmsandrewe heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT storekjan heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT mooresarah heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT altreemeryl heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT escherrobert heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT bardypeterg heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT suthersgraemek heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT dandrearichardj heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT horwitzmarshalls heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia AT scotthamishs heritablegata2mutationsassociatedwithfamilialmyelodysplasticsyndromeandacutemyeloidleukemia |