A summary of the FPD/AML RUNX1 mutants and the studies presented in this paper.

The FPD/AML RUNX1 mutants are listed in descending order of PEBP2/CBF activity. The Runt and transactivation domains are indicated on the mutant proteins as appropriate. Pedigrees 1 to 6 are from Song et al,10 and A1 and A2 are described in this paper. The results of the EMSA (DNA binding), affinity assay (PEBP2β/CBFβ subunit interaction), subcellular localization, and transactivation studies are summarized. The ratio of leukemic FPD individuals to FPD-affected individuals in each pedigree is indicated on the right. In the largest FPD/AML pedigrees, a markedly higher rate of leukemia is seen in the family with strong predicted dominant-negative K83E mutation (pedigree A1, dominant-negative, 57%) compared with the pedigree with a complete deletion of RUNX1 (pedigree 1, haploinsufficiency, 24%).