Switches from the lymphoid to myeloid lineage during B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment are considered rare and thus far have been detected in MLL-rearranged leukemia. Here, we describe a novel BCP-ALL subset, switching BCP-ALL or swALL, which demonstrated monocytosis early during treatment. Despite their monocytic phenotype, 'monocytoids' share immunoreceptor gene rearrangements with leukemic B lymphoblasts. All swALLs demonstrated BCP-ALL with CD2 positivity and no MLL alterations, and the proportion of swALLs cases among BCP-ALLs was unexpectedly high (4%). The upregulation of CEBPα and demethylation of the CEBPA gene were significant in blasts at diagnosis, prior to the time when most of the switching occurs. Intermediate stages between CD14(neg)CD19(pos)CD34(pos) B lymphoblasts and CD14(pos)CD19(neg)CD34(neg) 'monocytoids' were detected, and changes in the expression of PAX5, PU1, M-CSFR, GM-CSFR and other genes accompanied the switch. Alterations in the Ikaros and ERG genes were more frequent in swALL patients; however, both were altered in only a minority of swALLs. Moreover, switching could be recapitulated in vitro and in mouse xenografts. Although children with swALL respond slowly to initial therapy, risk-based ALL therapy appears the treatment of choice for swALL. SwALL shows that transdifferentiating into monocytic lineage is specifically associated with CEBPα changes and CD2 expression.

• MeSH
• antigeny CD2 imunologie   MeSH
• buněčný rodokmen MeSH
• dítě MeSH
• imunofenotypizace MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• monocyty patologie   MeSH
• multiplexová polymerázová řetězová reakce MeSH
• pre-B-buněčná leukemie imunologie   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• reziduální nádor MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH
• Názvy látek
• antigeny CD2 MeSH

• Klíčová slova
• Acute myeloid leukemia, Early T-cell precursor leukemia, KMT2A-AFDN, Lineage switch,
• MeSH
• akutní lymfatická leukemie farmakoterapie   genetika   patologie   MeSH
• akutní nemoc MeSH
• buněčný rodokmen genetika   MeSH
• genová přestavba MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• indukční chemoterapie metody   MeSH
• kineziny genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• malování chromozomů metody   MeSH
• mladiství MeSH
• myeloidní leukemie genetika   patologie   MeSH
• myosiny genetika   MeSH
• protoonkogenní protein MLL genetika   MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• Názvy látek
• AFDN protein, human MeSH Prohlížeč
• histonlysin-N-methyltransferasa MeSH
• kineziny MeSH
• KMT2A protein, human MeSH Prohlížeč
• myosiny MeSH
• protoonkogenní protein MLL MeSH

In the effort to improve immunophenotyping and minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL), the international Berlin-Frankfurt-Münster (iBFM) Flow Network introduced the myelomonocytic marker CD371 for a large prospective characterization with a long follow-up. In the present study, we aimed to investigate the clinical and biological features of CD371-positive (CD371pos) pediatric B-cell precursor ALL (BCP-ALL). From June 2014 to February 2017, 1812 pediatric patients with newly diagnosed BCP-ALLs enrolled in trial AIEOP-BFM ALL 2009 were evaluated as part of either a screening (n = 843, Italian centers) or validation cohort (n = 969, other iBFM centers). Laboratory assessment at diagnosis consisted of morphological, immunophenotypic, and genetic analysis. Response assessment relied on morphology, multiparametric flow cytometry (MFC), and polymerase chain reaction (PCR)-MRD. At diagnosis, 160 of 1812 (8.8%) BCP-ALLs were CD371pos. This correlated with older age, lower ETV6::RUNX1 frequency, immunophenotypic immaturity (all P < .001), and strong expression of CD34 and of CD45 (P < .05). During induction therapy, CD371pos BCP-ALLs showed a transient myelomonocytic switch (mm-SW: up to 65.4% of samples at day 15) and an inferior response to chemotherapy (slow early response, P < .001). However, the 5-year event-free survival was 88.3%. Among 420 patients from the validation cohort, 27 of 28 (96.4%) cases positive for DUX4-fusions were CD371pos. In conclusion, in the largest pediatric cohort, CD371 is the most sensitive marker of transient mm-SW, whose recognition is essential for proper MFC MRD assessment. CD371pos is associated to poor early treatment response, although a good outcome can be reached after MRD-based ALL-related therapies.

• MeSH
• buněčný rodokmen MeSH
• dítě MeSH
• imunofenotypizace MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pre-B-buněčná leukemie * genetika   mortalita   farmakoterapie   patologie   diagnóza   terapie   metabolismus   MeSH
• předškolní dítě MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• reziduální nádor * diagnóza   MeSH
• tetraspaniny genetika   metabolismus   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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• tetraspaniny MeSH

The differentiation of embryonic stem cells is associated with extensive changes in gene expression. It is not yet clear whether these changes are the result of binary switch-like mechanisms or that of continuous and progressive variation. Here, I have used immunostaining and single molecule RNA fluorescence in situ hybridization (FISH) to assess changes in the expression of the well-known pluripotency-associated gene Pou5f1 (also known as Oct4) and early differentiation markers Sox1 and T-brachyury in single cells during the early steps of differentiation of mouse embryonic stem cells. I found extensive overlap between the expression of Pou5f1/Sox1 or Pou5f1/T-brachyury shortly after the initiation of differentiation towards either the neuronal or the mesendodermal lineage, but no evidence of correlation between their respective expression levels. Quantitative analysis of transcriptional output at the sites of nascent transcription revealed that Pou5f1 and Sox1 were transcribed in pulses and that embryonic stem cell differentiation was accompanied by changes in pulsing frequencies. The progressive induction of Sox1 was further associated with an increase in the average size of individual transcriptional bursts. Surprisingly, single cells that actively and simultaneously transcribe both the pluripotency- and the lineage-associated genes could easily be found in the differentiating population. The results presented here show for the first time that lineage priming can occur in cells that are actively transcribing a pluripotent marker. Furthermore, they suggest that this process is associated with changes in transcriptional dynamics.

• Klíčová slova
• Early differentiation, Embryonic stem cells, Lineage priming, Single molecule RNA fluorescence in situ hybridization, Transcriptional dynamics,
• MeSH
• analýza jednotlivých buněk * MeSH
• buněčná diferenciace genetika   MeSH
• buněčný rodokmen genetika   MeSH
• embryonální kmenové buňky cytologie   metabolismus   MeSH
• fetální proteiny biosyntéza   genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• myši MeSH
• oktamerní transkripční faktor 3 biosyntéza   genetika   MeSH
• pluripotentní kmenové buňky cytologie   metabolismus   MeSH
• protein brachyurie MeSH
• proteiny T-boxu biosyntéza   genetika   MeSH
• transkripční faktory SOXB1 biosyntéza   genetika   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fetální proteiny MeSH
• oktamerní transkripční faktor 3 MeSH
• Pou5f1 protein, mouse MeSH Prohlížeč
• protein brachyurie MeSH
• proteiny T-boxu MeSH
• Sox1 protein, mouse MeSH Prohlížeč
• transkripční faktory SOXB1 MeSH

Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with early switch to the monocytic lineage and loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced switch detectable by flow cytometry (FC). Using exome and RNA sequencing, switch was found to positively correlate with three different genetic subtypes: PAX5-P80R mutation (5 cases with switch out of 5), rearranged DUX4 (DUX4r; 30 cases of 41) and rearranged ZNF384 (ZNF384r; 4 cases of 10). Expression profiles or phenotypic patterns correlated with genotypes, but within each genotype they could not identify cases who subsequently switched. If switching was not taken into account, the B-cell-oriented FC assessment underestimated the minimal residual disease level. For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the B-cell phenotype. Discordance on day 33 was observed in all the DUX4r, PAX5-P80R and ZNF384r subtypes. Importantly, despite the substantial phenotypic changes, possibly even challenging the appropriateness of BCP-ALL therapy, the monocytic switch was not associated with a higher incidence of relapse and poorer prognosis in patients undergoing standard ALL treatment.

• MeSH
• aktivátorový protein specifický pro B-buňky genetika   MeSH
• akutní lymfatická leukemie * MeSH
• B-lymfocyty MeSH
• imunofenotypizace MeSH
• lidé MeSH
• mutace MeSH
• pre-B-buněčná leukemie * diagnóza   genetika   MeSH
• reziduální nádor MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktivátorový protein specifický pro B-buňky MeSH
• PAX5 protein, human MeSH Prohlížeč

Interplay between conserved host specificity and occasional host switches is an important process determining the evolution of host-parasite systems. Here, we address the dynamics of host switches at the population level in rodent-associated Eimeria. Focusing mainly on two ecologically similar host groups, Murinae and Arvicolinae, we show that the Eimeria infecting those hosts form a complex system of many genetic lineages with different host specificities. The broad geographic distribution of lineages indicates that they are well-established genetic forms which retained their host specificities while spreading across large geographic areas. We also demonstrate that genetic structure is only partially reflected by morphological traits.

• Klíčová slova
• Arvicolinae, Coccidia, Coevolution, Host specificity, Murinae, Phylogeny,
• MeSH
• Arvicolinae MeSH
• Eimeria * MeSH
• fylogeneze MeSH
• hostitelská specificita MeSH
• interakce hostitele a parazita MeSH
• lidé MeSH
• Murinae MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Symbiotic bacterium closely related to the secondary symbiont of tsetse flies, Sodalis glossinidius, has been described from the bloodsucking fly Craterina melbae. Phylogenetic analysis of two genes, 16S rRNA gene and component of type three secretion system, placed the bacterium closer to the Sitophilus-derived branch of Sodalis than to the tsetse symbionts. This indicates that the Craterina-derived lineage of Sodalis originated independent of the tsetse flies symbionts and documents the capability of Sodalis bacteria either to switch between different host groups or to establish the symbiosis by several independent events.

• MeSH
• bakteriální geny MeSH
• bakteriální proteiny chemie   klasifikace   MeSH
• biologická evoluce MeSH
• Diptera mikrobiologie   MeSH
• Enterobacteriaceae klasifikace   izolace a purifikace   fyziologie   MeSH
• fylogeneze MeSH
• membránové glykoproteiny chemie   klasifikace   MeSH
• molekulární sekvence - údaje MeSH
• moucha tse-tse mikrobiologie   MeSH
• RNA ribozomální 16S chemie   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• symbióza * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• membránové glykoproteiny MeSH
• RNA ribozomální 16S MeSH
• S-layer proteins MeSH Prohlížeč

The Russula globispora lineage is a morphologically and phylogenetically well-defined group of ectomycorrhizal fungi occurring in various climatic areas. In this study we performed a multi-locus phylogenetic study based on collections from boreal, alpine and arctic habitats of Europe and Western North America, subalpine collections from the southeast Himalayas and collections from subtropical coniferous forests of Pakistan. European and North American collections are nearly identical and probably represent a single species named R. dryadicola distributed from the Alps to the Rocky Mountains. Collections from the southeast Himalayas belong to two distinct species: R. abbottabadensis sp. nov. from subtropical monodominant forests of Pinus roxburghii and R. tengii sp. nov. from subalpine mixed forests of Abies and Betula. The results suggest that speciation in this group is driven by a climate disjunction and adaptation rather than a host switch and geographical distance.

• Klíčová slova
• Biogeography, Climate, Disjunction, Ectomycorrhizal fungi, Evolutionary drivers, New taxa,
• Publikační typ
• časopisecké články MeSH

Differentiation during hematopoiesis leads to the generation of many cell types with specific functions. At various stages of maturation, the cells may change pathologically, leading to diseases including acute leukemias (ALs). Expression levels of regulatory molecules (such as the IKZF, GATA, HOX, FOX, NOTCH and CEBP families, as well as SPI-1/PU1 and PAX5) and lineage-specific molecules (including CD2, CD14, CD79A, and BLNK) may be compared between pathological and physiological cells. Although the key steps of differentiation are known, the available databases focus mainly on fully differentiated cells as a reference. Precursor cells may be a more appropriate reference point for diseases that evolve at immature stages. Therefore, we developed a quantitative real-time polymerase chain reaction (qPCR) array to investigate 90 genes that are characteristic of the lymphoid or myeloid lineages and/or are thought to be involved in their regulation. Using this array, sorted cells of granulocytic, monocytic, T and B lineages were analyzed. For each of these lineages, 3-5 differentiation stages were selected (17 stages total), and cells were sorted from 3 different donors per stage. The qPCR results were compared to similarly processed AL cells of lymphoblastic (n=18) or myeloid (n=6) origins and biphenotypic AL cells of B cell origin with myeloid involvement (n=5). Molecules characteristic of each lineage were found. In addition, cells of a newly discovered switching lymphoblastic AL (swALL) were sorted at various phases during the supposed transdifferentiation from an immature B cell to a monocytic phenotype. As demonstrated previously, gene expression changed along with the immunophenotype. The qPCR data are publicly available in the LeukoStage Database in which gene expression in malignant and non-malignant cells of different lineages can be explored graphically and differentially expressed genes can be identified. In addition, the LeukoStage Database can aid the functional analyses of next-generation sequencing data.

• Klíčová slova
• Acute leukemia, B and T lymphocytes, Differentiation plasticity, Gene expression, Hematopoiesis, Lineage promiscuity,
• MeSH
• akutní bifenotypická leukemie genetika   imunologie   patologie   MeSH
• B-lymfocyty imunologie   patologie   MeSH
• buněčná diferenciace genetika   MeSH
• buněčný rodokmen genetika   MeSH
• čipová analýza tkání MeSH
• hematopoéza genetika   MeSH
• imunofenotypizace MeSH
• lidé MeSH
• nádorové proteiny biosyntéza   MeSH
• regulace genové exprese u leukemie MeSH
• T-lymfocyty imunologie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové proteiny MeSH

Interspecific hybridization may result in asexual hybrid lineages that reproduce via parthenogenesis. Contrary to true parthenogens, sperm-dependent asexuals (gynogens and hybridogens) are restricted to the range of bisexual species, generally the parental taxa, by their need for a sperm donor. It has been documented that asexual lineages may rarely use sperm from a non-parental species or even switch a host. The available literature reports do not allow distinguishing, between whether such host switches arise by the expansion of asexuals out of their parental's range (and into that of another's) or by the local extinction of a parental population followed by a host switch. The present study combines new and previously collected data on the distribution and history of gynogenetic spined loaches (Cobitis) of hybrid origin. We identified at least three clonal lineages that have independently switched their sperm dependency to different non-parental Cobitis species, and in cases incorporated their genomes. Our current knowledge of European Cobitis species and their hybrids suggests that this pattern most probably results from the expansion of gynogenetic lineages into new areas. Such expansion was independent of the original parental species. This suggests that sperm dependence is not as restrictive to geographical expansion when compared with true parthenogenesis as previously thought.

• MeSH
• fylogeneze MeSH
• genotyp MeSH
• hybridizace genetická * MeSH
• máloostní genetika   MeSH
• mitochondriální DNA genetika   MeSH
• rozmnožování genetika   fyziologie   MeSH
• spermie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mitochondriální DNA MeSH