CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma.
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.
Fuchs
Ota
O
Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, 128 20 Prague 2, Czech Republic. Ota.Fuchs@uhkt.cz
Provaznikova
Dana
D
Kocova
Marcela
M
Kostecka
Arnost
A
Cvekova
Pavla
P
Neuwirtova
Radana
R
Kobylka
Petr
P
Cermak
Jaroslav
J
Brezinova
Jana
J
Schwarz
Jiri
J
Markova
Jana
J
Salaj
Peter
P
Klamova
Hana
H
Maaloufova
Jacqueline
J
Lemez
Petr
P
Novakova
Ludmila
L
Benesova
Katerina
K
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
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human