title: CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma.
abstract: The transcription factor CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor which is required for normal myeloid differentiation. C/EBPalpha is encoded by an intronless gene that is 2783 bp long and maps to human chromosome 19q13.1. C/EBPalpha is a member of the basic region leucine zipper (bZIP) class of DNA-binding proteins. The loss of function of C/EBPalpha 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) alpha) 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/EBPalpha mutations were detected in healthy donors (41 individuals). We discuss how these mutations can affect the cellular function of C/EBPalpha and block the myeloid differentiation.
authors.affiliation: Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, 128 20 Prague 2, Czech Republic. Ota.Fuchs@uhkt.cz
authors.forename: Ota
authors.initials: O
authors.lastname: Fuchs
authors.forename: Dana
authors.initials: D
authors.lastname: Provaznikova
authors.forename: Marcela
authors.initials: M
authors.lastname: Kocova
authors.forename: Arnost
authors.initials: A
authors.lastname: Kostecka
authors.forename: Pavla
authors.initials: P
authors.lastname: Cvekova
authors.forename: Radana
authors.initials: R
authors.lastname: Neuwirtova
authors.forename: Petr
authors.initials: P
authors.lastname: Kobylka
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.forename: Jana
authors.initials: J
authors.lastname: Brezinova
authors.forename: Jiri
authors.initials: J
authors.lastname: Schwarz
authors.forename: Jana
authors.initials: J
authors.lastname: Markova
authors.forename: Peter
authors.initials: P
authors.lastname: Salaj
authors.forename: Hana
authors.initials: H
authors.lastname: Klamova
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Maaloufova
authors.forename: Petr
authors.initials: P
authors.lastname: Lemez
authors.forename: Ludmila
authors.initials: L
authors.lastname: Novakova
authors.forename: Katerina
authors.initials: K
authors.lastname: Benesova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human