title: Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia.
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.
authors: Department of Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors: Christopher N
authors: CN
authors: Hahn
authors: Chan-Eng
authors: CE
authors: Chong
authors: Catherine L
authors: CL
authors: Carmichael
authors: Ella J
authors: EJ
authors: Wilkins
authors: Peter J
authors: PJ
authors: Brautigan
authors: Xiao-Chun
authors: XC
authors: Li
authors: Milena
authors: M
authors: Babic
authors: Ming
authors: M
authors: Lin
authors: Amandine
authors: A
authors: Carmagnac
authors: Young K
authors: YK
authors: Lee
authors: Chung H
authors: CH
authors: Kok
authors: Lucia
authors: L
authors: Gagliardi
authors: Kathryn L
authors: KL
authors: Friend
authors: Paul G
authors: PG
authors: Ekert
authors: Carolyn M
authors: CM
authors: Butcher
authors: Anna L
authors: AL
authors: Brown
authors: Ian D
authors: ID
authors: Lewis
authors: L Bik
authors: LB
authors: To
authors: Andrew E
authors: AE
authors: Timms
authors: Jan
authors: J
authors: Storek
authors: Sarah
authors: S
authors: Moore
authors: Meryl
authors: M
authors: Altree
authors: Robert
authors: R
authors: Escher
authors: Peter G
authors: PG
authors: Bardy
authors: Graeme K
authors: GK
authors: Suthers
authors: Richard J
authors: RJ
authors: D'Andrea
authors: Marshall S
authors: MS
authors: Horwitz
authors: Hamish S
authors: HS
authors: Scott
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D018076:DNA, Complementary; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006239:Haplotypes; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D010375:Pedigree; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
chemical_list: D018076:DNA, Complementary; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human