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

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) patientsʹ samples, 6/143 (4.2%) of MDS patientsʹ samples, 2/56 (3.6%) of non-Hodgkinʹs lymphoma (NHL) patientsʹ samples and 2/39 (5.1%) of multiple myeloma (MM) patientsʹ 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.