CEBPα mutations in childhood acute myeloid leukemia

CEBPα mutations have been described in adult acute myeloid leukemia (AML) and conferred a favorable prognosis. However, CEBPα mutation has not been reported in children. We investigated 117 children with de novo AML using DNA PCR assay followed by sequencing for each PCR product. CEBPα mutations were detected in seven patients, four had FAB M2, two M1 and one M4. CEBPα mutations only occurred in patients with intermediate cytogenetics and not in 56 children with AML1-ETO, CBFβ-MYH11, PML-RARα or MLL rearrangements. Five patients had mutations occurred in both N-terminal part and basic-leucine zipper (bZIP) domain, one had an N-terminal frameshift mutation and the remaining one had an inframe insertion in the bZIP domain. Cloning analysis on five samples carrying more than one mutations demonstrated one homozygous combined mutations and four heterozygous biallelic mutations. Four of seven CEBPα mutation(+) patients had cooperating mutations with FLT3-ITD or N-ras mutations compared to 27 in 109 CEBPα mutation(-) patients. Our results showed that CEBPα mutations occurred in 6% of childhood AML and most exhibited combined mutations in both N-terminal part and bZIP domain.