Carolyn M. Butcher

Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia

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.

A tale of two siblings: two cases of AML arising from a single pre-leukemic DNMT3A mutant clone.

A tale of two siblings: two cases of AML arising from a single pre-leukemic DNMT3A mutant clone

Clonal and lineage analysis of somatic DNMT3A and JAK2 mutations in a chronic phase polycythemia vera patient.

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RUNX1 mutations are rare in chronic phase polycythaemia vera.

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