Further evidence that germline CEBPA mutations cause dominant inheritance of acute myeloid leukaemia

Another pedigree with familial acute myeloid leukemia and germline CEBPA mutation

“…2,3 Moreover, the germline mutation reported here is strictly identical to the germline mutation reported by Sellick et al, 3 suggesting that this region of CEBPA is probably unstable (Table 1). However, acquired mutations in this region have been rarely described and, to our knowledge, remission samples were not tested to exclude a germline mutation.…”

“…[2][3][4] Like in most of the previously reported patients with germline CEBPA mutation that could have been analyzed at somatic level, 2-6 patients I:2 and II:2 exhibited a second CEBPA mutation without other detectable molecular abnormality in the leukemic cells. These findings suggest that the N-terminal germline CEBPA mutation seems to promote the occurrence of an additional C-terminal mutation in CEBPA, which may represent the second genetic event in AML pathogenesis.…”

“…1 Recently, four families have been independently described with several members affected by AML and carrying a germline CEBPA mutation. [2][3][4][5][6] Here, we report the clinical and biological features of two members of a novel family in which a germline CEBPA mutation predisposed to develop AML ( Figure 1a). …”

Transcriptional dysregulation during myeloid transformation in AML

“…Three families have recently been reported in whom three, four and two members affected by AML carried germline heterozygous CEBPA mutations (Smith et al, 2004;Sellick et al, 2005;Nanri et al, 2006). Several aspects are remarkable to these observations.…”

Mutation of C/EBPα predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen

“…These mutations are clustered either in the N-terminal third or in the C-terminal part of the protein, where they lead to production of the truncated p30 form of C/EBP␣ or to C/EBP␣ variants deficient in DNA binding, respectively. [9][10][11][12][13][14][15][16][17][18] Very little information is available regarding which genetic lesions collaborate with CEBPA mutants, although an association with 9q deletions has been reported. 19 The critical genes have, however, not been identified.…”