The most important reason for therapy failure in pediatric acute myeloid leukemia (AML) is relapse. In order to identify miRNAs that contribute to the clonal evolution towards relapse in pediatric AML, miRNA expression profiling of 127 de novo pediatric AML cases were used. In the diagnostic phase, no miRNA signatures could be identified that were predictive for relapse occurrence, in a large pediatric cohort, nor in a nested mixed lineage leukemia (MLL)-rearranged pediatric cohort. AML with MLL- rearrangements are found in 15-20% of all pediatric AML samples, and reveal a relapse rate up to 50% for certain translocation partner subgroups. Therefore, microRNA expression profiling of six paired initial diagnosis-relapse MLL-rearranged pediatric AML samples (test cohort) and additional eight paired initial diagnosis-relapse samples with MLL-rearrangements (validation cohort) was performed. A list of 53 differentially expressed miRNAs was identified of which the miR-106b~25 cluster, located in intron 13 of MCM7, was the most prominent. These differentially expressed miRNAs however could not predict a relapse in de novo AML samples with MLL-rearrangements at diagnosis. Furthermore, higher mRNA expression of both MCM7 and its upstream regulator E2F1 was found in relapse samples with MLL-rearrangements. In conclusion, we identified the miR-106b~25 cluster to be upregulated in relapse pediatric AML with MLL-rearrangements.

• Klíčová slova
• MLL, acute myeloid leukemia, miR-106b~25, relapse,
• MeSH
• akutní myeloidní leukemie genetika   patologie   MeSH
• dítě MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• introny genetika   MeSH
• karcinogeneze genetika   MeSH
• klonální evoluce MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   patologie   MeSH
• MCM komplex, komponenta 7 metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• mikro RNA genetika   MeSH
• mladiství MeSH
• multigenová rodina MeSH
• předškolní dítě MeSH
• protoonkogenní protein MLL genetika   MeSH
• regulace genové exprese u leukemie * MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktor E2F1 metabolismus   MeSH
• translokace genetická MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• E2F1 protein, human MeSH Prohlížeč
• histonlysin-N-methyltransferasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• MCM komplex, komponenta 7 MeSH
• MCM7 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• mikro RNA MeSH
• MIRN106 microRNA, human MeSH Prohlížeč
• protoonkogenní protein MLL MeSH
• transkripční faktor E2F1 MeSH

DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.

• Klíčová slova
• Chromosome Section, DNA replication, RecQ helicases, minichromosome maintenance proteins,
• MeSH
• apoptóza MeSH
• chromatin genetika   MeSH
• helikasy RecQ genetika   metabolismus   MeSH
• imunoenzymatické techniky MeSH
• imunoprecipitace MeSH
• interakční proteinové domény a motivy MeSH
• kur domácí genetika   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• MCM komplex, komponenta 2 genetika   metabolismus   MeSH
• MCM komplex, komponenta 7 genetika   metabolismus   MeSH
• MCM proteiny genetika   metabolismus   MeSH
• messenger RNA genetika   MeSH
• molekulární sekvence - údaje MeSH
• nádorové buňky kultivované MeSH
• nádory kostí genetika   metabolismus   patologie   MeSH
• osteosarkom genetika   metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• povrchová plasmonová rezonance MeSH
• proliferace buněk MeSH
• průtoková cytometrie MeSH
• replikace DNA * MeSH
• replikační počátek genetika   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin MeSH
• helikasy RecQ MeSH
• MCM komplex, komponenta 2 MeSH
• MCM komplex, komponenta 7 MeSH
• MCM proteiny MeSH
• MCM10 protein, human MeSH Prohlížeč
• MCM2 protein, human MeSH Prohlížeč
• MCM7 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• RECQL4 protein, human MeSH Prohlížeč