The t(X;21) fuses AML1 to FOG2. (A) FISH with paints for chromosomes X (green) and 21 (red) confirms t(X;21). (B) FISH with the AML1 probe (red) hybridizes not only to both copies of chromosome 21 but also aberrantly to a third chromosome (indicated by arrow). (C) AML1-FOG2 fuses AML1 nt 805 to FOG2 nt 557 and encodes a chimeric protein composed of AML1 aa 1-268 fused to FOG2 aa 178-1151. (D) Structures for the chimeric fusion proteins are shown relative to those for AML1 and FOG2. AML1-FOG2 retains the DNA-binding domain (DBD; blue boxes) of AML1 plus the 8 zinc finger domains (▦) and CtBP interaction domain (CID; red boxes) of FOG2, whereas FOG2-AML1 retains the activation domain (AD; green boxes) of AML1. The fusion breakpoints are indicated by arrows. (E) Model for transcriptional repression of CBF target genes in which AML1-FOG2 binds the promoter via the DBD from AML1 but aberrantly recruits the CtBP corepressor complex (GTF, general transcription factors). (F) Model for transcriptional repression of GATA1 target genes in which AML1-FOG2 binds the promoter via interaction with GATA1 but aberrantly recruits the CtBP corepressor complex.