Sequence variations in the zinc-finger domains of GATA2 in myeloid malignancies. (A) Schematic representation of the human GATA2 gene and protein. The GATA2 gene consists of 6 exons. The coding exons (exon 2-6) are depicted in black and the 5′ and 3′ untranslated regions are depicted in gray. The GATA2 gene has 3 transcript variants that encode for 2 different protein isoforms with the same translation start site in exon 2. Isoform 1, encoded by transcript variant 1 or 2, contains 480 amino acids (50.5 kDa). Isoform 2, encoded by transcript variant 3, contains a smaller fifth exon resulting in a protein of 466 amino acids (49.1 kDa). Transcript variant 2, in which transcription is initiated from a distal first exon (1S), is specific for hematopoietic and neuronal cells. The encoded protein has 2 transactivation domains (TAD), a negative regulatory domain (NRD), a nuclear localization signal (N), and 2 zinc-finger domains (ZF). (B) Acquired mutations and sequence variations in the N-terminal (N-ZF) and C-terminal (C-ZF) zinc-finger domain of GATA2 in myeloid malignancies. Sequence variations in pediatric AML from the present study are depicted in black. Previously reported mutations in adult AML with FAB-M5 morphology or in blast crisis of CML are depicted in white and gray, respectively.^26,27  Each symbol represents an independent GATA2 mutation or variation. Numbers indicate the amino acid affected by each mutation or variation. The type of mutation is indicated by the symbol.