CCAAT/enhancer binding protein-alpha (CEBPA) belongs to a family of leucine zipper transcription factors necessary for late differentiation events of many cell types. CEBPA gene has recently been recognized as the target of genetic alterations in acute myeloid leukemia (AML). CEBPA mutations and polymorphisms were determined in a large series of Southeast Asian AML (n = 247) using polymerase chain reaction and direct sequencing. Chromosome and FLT3 mutation analyses were also undertaken. Thirtytwo distinct types of nucleotide changes (7 known and 25 novel mutations) were identified in 34 cases (13.8%). Three types of polymorphisms were found in 60 cases (24.3%) including a novel nt1401C>T polymorphism. All polymorphisms were located at the C-terminal region whereas the majority of mutations (62.5%) occurred at the N-terminal region. The most common polymorphism was the nt1175_1180dup resulting in the predicted P194_H195 duplication protein in 50 cases. Although CEBPA mutations were predominantly associated with a normal karyotype (76%), 15.7% of patients with an unfavorable risk and 4.3% of patients with a favorable risk also had the mutations. Moreover, CEBPA polymorphisms were similarly found across all cytogenetic risk groups and occurred in all leukemia subtypes. FLT3 mutations were comparably discovered among patients with CEBPA mutations, polymorphisms and wild-type (26-30%). In conclusion, CEBPA polymorphisms occurred more frequently than CEBPA mutations and could be identified across all prognostic risk groups. The high occurrence of CEBPA polymorphisms should be recognized in order not to include this group of patients with CEBPA polymorphisms for prognostic evaluation of CEBPA mutations in any clinical trials.

AML1 mutations were identified in 6.3% of AML patients with chromosomal translocations involving CBF, PML-RARα α, HOX, or ETS transcription factor (TF) gene families. Rare chromosomal abnormalities, t(16;21) and t(7;11), were also found. This study represents the first series to demonstrate the coexistence of known and novel AML1 mutations with different TF gene mutations. Although the occurrence of two TF gene mutations may appear unnecessary, the possible synergistic mechanism between different TF gene families cannot be excluded and needs to be further explored. Haematologica 2007; 92:861-862