Heritable GATA2 Mutations Associated with Familial Myelodysplastic Syndrome and Acute Myeloid Leukemia
By C. Hahn, C. Chong, C. Carmichael, E. Wilkins, Peter J. Brautigan, Xiaochun Li, Milena Babic, Ming Lin, A. Carmagnac, Young K. Lee and 18 more. Nature Genetics, 2011
610 citations recorded by the source corpus.
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.
Subfields: Genetics, Hematology
View Paper: https://www.semanticscholar.org/paper/20a737906d7fb456d387784c00d62f640f780d2d
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Citations in the corpus
- GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. (2014, background): “The genetic lesions in GATA2 are also heterogeneous, clustering into three different groups: missense mutations and in-frame deletions involving the C-terminal zinc finger; nonsense mutations, frameshifts, and large gene deletions predicted to result in null alleles; and regulatory mutations within ”
- Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. (2013, background): “Especially in young patients, collection of family history should focus on conditions suggestive of inherited bone marrow failure disorders, such as Fanconi anemia and telomere disorders.(20-24) A complete physical examination should follow including spleen size.”
- A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. (2014, background): “…GATA2 DNA-binding domains or in GATA2 regulatory sequences represents a well-established underlying cause of MDS/AML and Emberger/MonoMAC syndromes (Hahn et al., 2011; Hsu et al., 2013; Hsu et al., 2011; Ostergaard et al., 2011; Rodrigues (F) Immunophenotyping of control and enhancer-targeted…”