National Repository of Grey Literature 26 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Epigenetic factors CTCF a SMARCA5 control expression of hematopoietic transcription factor SPI1 in cells of acute myeloid leukemia and myelodysplastic syndrome.
Dluhošová, Martina ; Stopka, Tomáš (advisor) ; Machová Poláková, Kateřina (referee) ; Kozák, Tomáš (referee)
CCCTC-binding factor (CTCF) can both activate as well as inhibit transcription by forming chromatin loops between regulatory regions and promoters. In this regard, Ctcf binding on the non-methylated DNA and its interaction with the Cohesin complex results in differential regulation of the H19/Igf2 locus. Similarly, a role for CTCF has been established in normal hematopoietic development; however its involvement, despite mutations in CTCF and Cohesin complex were identified in leukemia, remains elusive. CTCF regulates transcription dependently on DNA methylation status and can if bound block interactions of enhancers and promoters. Here, we show that in hematopietic cells CTCF binds to the imprinting control region of H19/Igf2 and found that chromatin remodeller Smarca5, which also associates with the Cohesin complex, facilitates Ctcf binding and regulatory effects. Furthermore, Smarca5 supports CTCF functionally and is needed for enhancer-blocking effect at imprinting control region. We identified new CTCF-recognized locus near hematopoietic regulator SPI1 (PU.1) in normally differentiating myeloid cells together with members of the Cohesin complex. Due to DNA methylation, CTCF binding to the SPI1 gene is reduced in AML blasts and this effect was reversible by DNA methylation inhibitor 5-azacitidine.
Experimental therapy of B-cell Non-Hodgkin's lymphonas.
Klánová, Magdalena ; Klener, Pavel (advisor) ; Machová Poláková, Kateřina (referee) ; Froňková, Eva (referee)
1 ABSTRACT B-cell non-Hodgkin lymphomas (B-NHL) represent the most common mature lymphoproliferative diseases. B-NHL arise at different stages of B-cell development and represent their malignant counterpart. Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are aggressive types of B-NHLs. Deregulation of cell cycle control, inhibition of apoptosis or abnormal DNA damage response play a key role in the pathogenesis of DLBCL and MCL. Aberrant activation of several signaling pathways that further promote survival, cell proliferation or affect the tumor microenvironment have been recently recognized. Increased understanding of the oncogenic mechanisms implicated in pathogenesis of B-NHL lead to development of novel agents that target the oncogenic drivers of distinct lymphoma subtypes. MCL is an aggressive subtype of B-NHL associated with poor prognosis. In vivo models of human MCL for experimental therapy are however scarce. We established and characterized several mouse models of human MCL by xenotransplantation of either primary cells or established cell lines into immunodeficient mice (publication no 1). We demonstrated that engrafted MCL cells displayed complex changes of gene expression profile, phenotype and sensitivity to cytotoxic agents compared to the original in vitro growing...
Prokaryotic symbionts of free-living anaerobic protists
Poláková, Kateřina ; Čepička, Ivan (advisor) ; Hampl, Vladimír (referee)
Anaerobní prvoci jsou organismy obývající ředí bez přítomnosti kyslíku. Najdeme je anoxických habitatech jako jsou mořské a sladkovodní sedimenty, komunální skládky, nesmíme opomenout zástupce žijící v bachoru přežvýkavců, trávicím traktu švábů a dalších živočichů. Většinou mají anaerobní deriváty mitochondrií, často hydrogenosomy, organely produkující vodík. Metabolismus anaerobních prvoků je ve srovnání s aerobními organismy méně efektivní Časté interakce anaerobních ický my však mohou Symbiózy mezi anaerobními běžné a vznikly u zástupců mnoha anaerobních linií. žít buď endosymbioticky, uvnitř buňky hostitele, nebo ektosymbioticky, na povrchu hostitelské buňky. Dvě ekologicky významné skupiny prokaryot si dokázaly osvojit život symbiotickém vztahu volně žijícími anaerobními prvoky anogenní archebakterie, osídlující hlavně , využívají vodík nické sloučeniny k anu a síran redukující bakterie, žijící hlavně na povrchu buněk, využívají vodík a různé organické sloučeniny k redukci síranu na sulfan. Velmi málo se ví o bližším charakteru těchto vztahů druhové identitě a hostitelské specifitě prokaryotických symbiontů. Další výzkum je nutný pro pochopení fenoménu symbióz v anoxickém světě. Klíčová slova: anaerobní prvoci symbióza anogenní archebakterie síran redukující bakterie
Lineage plasticity of leukemic cells
Slámová, Lucie ; Mejstříková, Ester (advisor) ; Brdička, Radim (referee) ; Machová Poláková, Kateřina (referee)
So far, the lymphoid to myeloid lineage switch during the treatment of B cell precursor acute lymphoblastic leukemia (BCP ALL) was identified only rarely in patients with the MLL gene rearrangement. We discovered a novel BCP ALL subset switching to monocytoid lineage during an early phase of the treatment - swALL ("switching" ALL) with no MLL gene rearrangement. The proportion of swALL cases among BCP ALLs was unexpectedly high (3-4%). All swALLs have expressed the CD2 antigen (LFA-2). The upregulation of C/EBPα gene and hypomethylation of the CEBPA promoter were significant in blasts already at diagnosis, proceeding the lineage switch in the majority of the cases. SwALL patients were characterized by unique subpopulation of the cells coexpressing B lymphoid and monocytoid markers. Changes in the gene expression of M-CSFR, GM- CSFR and other genes accompanied the lineage switch. The lineage switch could be recapitulated in vivo and in vitro. Even if the children patient with swALL respond slowly to initial therapy, the prognosis is comparable to "other" BCP ALLs. Risk-based ALL therapy appears to be the treatment of choice for swALL. Powered by TCPDF (www.tcpdf.org)
Delineating aggressiveness of acute myeloid leukemia in a mouse model carrying mutations of Spil (PU.1) and Trp53.
Bašová, Petra ; Stopka, Tomáš (advisor) ; Machová Poláková, Kateřina (referee) ; Zuna, Jan (referee)
PU.1 downregulation within haematopoietic stem and progenitor cells (HSPCs) is the primary mechanism for the development of acute myeloid leukaemia (AML) in mice with homozygous deletion of the upstream regulatory element (URE) of PU.1 gene. p53 is a well known tumor suppressor that is often mutated in human haematologic malignancies including AML and adds to their aggressiveness; however its genetic deletion does not cause AML in mouse. Deletion of p53 in the PU.1ure/ure mice (PU.1ure/ure p53-/- ) results in more aggressive AML with shortened overall survival. PU.1ure/ure p53-/- progenitors express significantly lower PU.1 levels. In addition to URE deletion we searched for other mechanisms that in absence of p53 contribute to decreased PU.1 levels in PU.1ure/ure p53-/- mice. We found involvement of Myb and miR-155 in downregulation of PU.1 in aggressive murine AML. Upon inhibition of either Myb or miR-155 in vitro the AML progenitors restore PU.1 levels and lose leukaemic cell growth similarly to PU.1 rescue. The MYB/miR-155/PU.1 axis is a target of p53 and is activated early after p53 loss as indicated by transient p53 knockdown. Furthermore, deregulation of both MYB and miR-155 coupled with PU.1 downregulation was observed in human AML, suggesting that MYB/miR-155/PU.1 mechanism may be involved...
Regulation of DLX1 gene expression through AP-1 binding site
Rejlová, Kateřina ; Starková, Júlia (advisor) ; Machová Poláková, Kateřina (referee)
Regulation of expression DLX1 gene, whose elevated levels are detected in patients with acute myeloid leukemia with FLT3-ITD mutations, is not still completely explored topic. The first aim of this study was to determine which selected signaling pathways regulate gene expression of DLX1. ERK a JNK pathways were selected by using qRT-PCR and western blot. These pathways cause activation of the transcription factor AP-1 subunits, the AP-1 putative promoter binding site was identified also in the promoter of the DLX1 gene. The second aim of this study was to test the hypothesis on the regulation of gene expression of DLX1 (via ERK/JNK pathway) through AP-1 binding site on the promoter. Dual luciferase assay using luminescent luciferase activity was performed to test this hypothesis. Gene of the luciferase is contained in the used luciferase vector. The short and the long part of the DLX1 promoter (around AP-1 site) were inserted before the gene of the luciferase in the constructs used in this method. The results of this study indicate that the regulation of gene expression through AP-1 promoter binding site is important but not sufficient part of the regulatory cascade running through ERK and JNK pathway. There must be another transcription factors activated by ERK1/2 kinase which are probably also involved in...
Role of the oncogenic microRNAs miR-17-92 and miR-155 in the regulation of hematopoietic differentiation and leukemogenesis
Pospíšil, Vít ; Stopka, Tomáš (advisor) ; Pospíšek, Martin (referee) ; Machová Poláková, Kateřina (referee)
(English version): Hematopoietic differentiation is highly ordered multistep process, where generation of terminal blood cells is dependent upon coordinated regulation of gene expression by key regulators: transcription factors and mikroRNAs. PU.1 (Sfpi1) is a versatile hematopoetic transcription factor required for the proper generation of both myeloid and lymphoid lineages. MikroRNAs represent a novel class of ~22 nucleotide long non-coding posttranscriptional regulators that inhibit expression of genes by blocking protein translation or by mRNA degradation. In this PhD thesis I present research data documenting novel mechanisms of regulation and function of two oncogenic mikroRNAs, miR-17-92 cluster and miR-155 and myeloid transcriptional factors PU.1 upon macrophage differentiation of myeloid progenitors. The miR-17-92 cluster (Oncomir1) encodes seven related mikroRNAs that regulate cell proliferation, apoptosis and development and is overexpressed in number of malignancies including myeloid leukemia. Presented PhD thesis documents novel macrophage specific regulatory mechanisms involving the oncogenic cluster miR-17-92. Using transgenic PU.1-/- myeloid progenitors we show that upon macrophage differentiation, the transcription factor PU.1 induces the secondary determinant, the transcription...
The role of transcription factors PU.1 a GATA-1 during leukemia differentiation.
Burda, Pavel ; Stopka, Tomáš (advisor) ; Kořínek, Vladimír (referee) ; Machová Poláková, Kateřina (referee)
Hematopoiesis is coordinated by a complex regulatory network of transcription factors among them PU.1 (Spi1, Sfpi1) and GATA-1 represent key molecules. GATA-1 and PU.1 bind each other on DNA to block each others transcriptional programs to prevent development of undesired lineage during hematopoietic commitment. Murine erythroleukemia (MEL) cells, transformed erythroid precursors that are blocked from completing the late stages of erythroid differentiation, co-express GATA-1 and PU.1 and as my and others data document, are able to respond to molecular removal (down-regulation) of PU.1 or addition (up-regulation) of GATA-1 by inducing terminal erythroid differentiation. We provide novel evidence that downregulation of GATA-1 or upregulation of PU.1 induces incompletely differentiation into cell cycle arrested monocytic-like cells. Furthermore, PU.1- dependent transcriptome is negatively regulated by GATA-1 in MEL cells, including CCAAT/enhancer binding protein alpha (Cebpa) and Core-binding factor, beta subunit (Cbfb) that encode additional key hematopoietic transcription factors. Chromatin immunoprecipitation and reporter assays identified PU.1 motif sequences near Cebpa and Cbfb that are co-occupied by PU.1 and GATA-1 in the leukemic blasts. Furthermore, transcriptional regulation of these loci by...

National Repository of Grey Literature : 26 records found   1 - 10nextend  jump to record:
See also: similar author names
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18 Poláková, KATEŘINA
2 Poláková, Kamila
2 Poláková, Katarína
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1 Poláková, Klára
2 Poláková, Kristína
6 Poláková, Kristýna
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