OBJECTIVES: The impact of modern prognostic markers on clinical course of chronic lymphocytic leukaemia (CLL) in everyday practice has been not yet well defined, especially in large series of patients. Therefore, the goal of this study was to assess the influence of conventional as well as modern prognostic factors on overall survival (OS) and time to therapy (TTT) of patients with CLL. METHODS: We retrospectively analysed data of all patients consecutively entered into the databases of five large academic centres in the Czech Republic. The total of 1300 patients was included in the analysis. RESULTS AND CONCLUSION: Through the use of uniparametric analysis, it was determined that gender, clinical stage Rai II-IV, unmutated IgVH status, deletion 17p (for both 5% and 20% cut-off), deletion 11q, ZAP-70 positivity and high expression of CD38 had significant negative influence on OS. TTT was significantly influenced by gender, Rai stage, IgVH status, deletion 11q, deletion 17p, deletion 13q and CD38 expression. Multiparametric analysis revealed that OS was significantly influenced by gender, age, IgVH status and deletion 17p. If only patients who died of CLL were included, gender, age, Rai stage, IgVH status and deletion 17p had significant influence on OS. Based on our results, the examination of biological prognostic markers can give an insight into the possible disease evolution in daily clinical practice. Biological prognostic markers are, however, not ready (maybe except deletion 17p in younger patients) to be used for guidance of therapy at least outside of clinical trials.

• MeSH
• analýza přežití MeSH
• antigeny CD38 krev   MeSH
• chromozomální delece MeSH
• chronická lymfatická leukemie etiologie   genetika   imunologie   patologie   MeSH
• difúzní velkobuněčný B-lymfom etiologie   MeSH
• dospělí MeSH
• geny pro těžké řetězce imunoglobulinů MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 17 genetika   MeSH
• membránové glykoproteiny krev   MeSH
• mutace MeSH
• nádorové biomarkery krev   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protein-tyrosinkináza ZAP-70 krev   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• lidé MeSH
• mnohočetný myelom genetika   MeSH
• molekulární sekvence - údaje MeSH
• myelodysplastické syndromy genetika   MeSH
• nehodgkinský lymfom genetika   MeSH
• proteiny vázající zesilovač transkripce CCAAT genetika   MeSH
• repetitivní sekvence nukleových kyselin genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční delece MeSH
• substituce aminokyselin genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

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.

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• dospělí MeSH
• financování organizované MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutace MeSH
• myelodysplastické syndromy genetika   MeSH
• nehodgkinský lymfom genetika   MeSH
• polymorfismus genetický MeSH
• proteiny vázající zesilovač transkripce CCAAT genetika   chemie   MeSH
• sekvence aminokyselin MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH