A family harboring a germ-line N-terminal C/EBPα mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPα mutation

✍ Scribed by Tomoko Nanri; Naokuni Uike; Toshiro Kawakita; Eisaku Iwanaga; Hiroaki Mitsuya; Norio Asou

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 232 KB
• Volume: 49
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.20734

✦ Synopsis

Abstract

C/EBPα plays an essential role as a transcription factor in myeloid cell differentiation. Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4‐base pair insertion in the N‐terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107). The father and a son at diagnosis of AML had different in‐frame insertion mutations in the C‐terminal region of C/EBPα. These C‐terminal mutations disappeared upon remission in both patients. Interestingly, the father showed different in‐frame insertion mutations in the C‐terminal CEBPA at the time of diagnosis and relapse. These data strongly suggest that the N‐terminal C/EBPα mutation predisposes to the occurrence of a C‐terminal C/EBPα mutation as a secondary genetic hit, causing AML. © 2009 Wiley‐Liss, Inc.