CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma

• Published in: Blood cells, molecules, & diseases Vol. 40; no. 3; pp. 401 - 405
• Main Authors: Fuchs, Ota, Provaznikova, Dana, Kocova, Marcela, Kostecka, Arnost, Cvekova, Pavla, Neuwirtova, Radana, Kobylka, Petr, Cermak, Jaroslav, Brezinova, Jana, Schwarz, Jiri, Markova, Jana, Salaj, Peter, Klamova, Hana, Maaloufova, Jacqueline, Lemez, Petr, Novakova, Ludmila, Benesova, Katerina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2008
• Subjects: Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; CCAAT-Enhancer-Binding Proteins - chemistry; CCAAT-Enhancer-Binding Proteins - genetics; CEBPA mutations; Female; Humans; Leukemia, Myeloid, Acute - genetics; Lymphoma, Non-Hodgkin - genetics; Male; Middle Aged; Molecular Sequence Data; Multiple myeloma; Multiple Myeloma - genetics; Mutation; Myelodysplastic syndrome; Myelodysplastic Syndromes - genetics; Non-Hodgkin's lymphoma; Polymorphism, Genetic; CEBPA mutations; Non-Hodgkin's lymphoma; Acute myeloid leukemia; Myelodysplastic syndrome; Multiple myeloma
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2007.11.005

The transcription factor CCAAT/enhancer binding protein (C/EBP)α is a myeloid-specific transcription factor which is required for normal myeloid differentiation. C/EBPα is encoded by an intronless gene that is 2783 bp long and maps to human chromosome 19q13.1. C/EBPα is a member of the basic region leucine zipper (bZIP) class of DNA-binding proteins. The loss of function of C/EBPα has leukemogenic potential. Four types of polymorphisms and 25 mutations (3 already known mutations and 22 novel mutations) were detected in CEBPA (gene for the transcription factor CCAAT/enhancer binding protein (C/EBP) α) in analysed samples from 390 patients with myelodysplastic syndrome (MDS) and hematologic malignancies. CEBPA mutations were found in 14/152 (9.2%) of acute myeloid leukemia (AML) patients' samples, 6/143 (4.2%) of MDS patients' samples, 2/56 (3.6%) of non-Hodgkin's lymphoma (NHL) patients' samples and 2/39 (5.1%) of multiple myeloma (MM) patients' samples. No C/EBPα mutations were detected in healthy donors (41 individuals). We discuss how these mutations can affect the cellular function of C/EBPα and block the myeloid differentiation.