A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies

Hereditary mutations associated with hematologic malignancies are rare. Het erozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial pla telet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation mal e. After allogeneic stem cell transplantation from his human leukocyte anti gen-identical sister, a donor-derived, genetically identical leukemia devel oped in the recipient and the donor. Sequencing analysis identified a G-to- T transition within the CBFA2 gene, which involves codon 198, encoding a co nserved aspartic acid within the DNA-binding Runt domain. Three of 5 siblin gs affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation anal ysis of the CBFA2 gene before sibling allogeneic transplantation in familie s with FPD/AML. (C) 2001 by The American Society of Hematology.