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1. Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice

Author

Bögeholz, N, Pauls, P, Kaese, S, Schulte, JS, Lemoine, MD, Dechering, DG, Frommeyer, G, Goldhaber, JI, Seidl, MD, Kirchhefer, U, Eckardt, L, Müller, FU, and Pott, C

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Heart Disease, Cardiovascular, Action Potentials, Animals, Calcium, Calcium Signaling, Female, Gene Expression, Heart Atria, Male, Membrane Potentials, Mice, Mice, Transgenic, Myocardial Contraction, Myocardium, Myocytes, Cardiac, Sarcoplasmic Reticulum, Sodium-Calcium Exchanger, Na+/Ca2+ exchanger, Afterdepolarizations, Atrial fibrillation, Atrial myocytes, Na(+)/Ca(2+) exchanger, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Biochemistry and cell biology, Cardiovascular medicine and haematology, Medical physiology
Abstract

AimsIn atrial fibrillation, increased function of the Na+/Ca2+-exchanger (NCX) is one among several electrical remodeling mechanisms.Methods/resultsUsing the patch-clamp- and Ca2+ imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2+ extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18±0.05; WTOE:0.02±0.02; p

Published
2016

6. EuroClonality-NGS Recommendations for Evaluation of B-Cell Clonality Analysis by Next-Generation Sequencing: A Structured Approach with the DEPART Algorithm.

Author

Brand, M. van den, Möbs, M., Otto, F., Kroeze, L.I., Gonzalez de Castro, D., Stamatopoulos, K., Davi, F., Bravetti, C., Kolijn, P.M., Vlachonikola, E., Stewart, J.P., Pott, C., Hummel, M., Darzentas, N., Langerak, A.W., Fend, F., Groenen, P.J.T.A., Brand, M. van den, Möbs, M., Otto, F., Kroeze, L.I., Gonzalez de Castro, D., Stamatopoulos, K., Davi, F., Bravetti, C., Kolijn, P.M., Vlachonikola, E., Stewart, J.P., Pott, C., Hummel, M., Darzentas, N., Langerak, A.W., Fend, F., and Groenen, P.J.T.A.

Abstract

Contains fulltext : 296673.pdf (Publisher’s version ) (Open Access), Next-generation sequencing (NGS)-based clonality analysis allows in-depth assessment of the clonal composition of a sample with high sensitivity for detecting small clones. Within the EuroClonality-NGS Working Group, a protocol for NGS Ig clonality analysis was developed and validated previously. This NGS-based approach was designed to generate small amplicons, making it suitable for samples with suboptimal DNA quality, especially material derived from formalin-fixed, paraffin-embedded tissue. Using expert assessment of NGS Ig clonality results as a reference, a structured algorithmic approach to the assessment of NGS-amplicon-based B-cell clonality analysis was developed. A structured approach with the Detection of clonality through Evaluation of sample quality and assessment of Pattern, Abundance and RaTio (DEPART) algorithm was proposed, which consecutively evaluates sample quality, the pattern of the clonotypes present, the abundance of the most dominant clonotypes, and the ratio between the dominant clonotypes and the background to evaluate the different Ig gene targets. Specific issues with respect to evaluation of the various Ig targets as well as the integration of results of individual targets into a molecular clonality conclusion are discussed and illustrated with case examples. Finally, the importance of interpretation of NGS-based clonality results in clinical and histopathologic contexts is discussed. It is expected that these recommendations will have clinical utility to facilitate proper evaluation of clonality assessment.

Published
2023

8. Standardization of molecular monitoring of CML : results and recommendations from the European treatment and outcome study

Author

White HE, Salmon M, Albano F, Andersen CSA, Balabanov S, Balatzenko G, Barbany G, Cayuela JM, Cerveira N, Cochaux P, Colomer D, Coriu D, Diamond J, Dietz C, Dulucq S, Engvall M, Franke GN, Gineikiene-Valentine E, Gniot M, Gómez-Casares MT, Gottardi E, Hayden C, Hayette S, Hedblom A, Ilea A, Izzo B, Jiménez-Velasco A, Jurcek T, Kairisto V, Langabeer SE, Lion T, Meggyesi N, Mešanović S, Mihok L, Mitterbauer-Hohendanner G, Moeckel S, Naumann N, Nibourel O, Oppliger Leibundgut E, Panayiotidis P, Podgornik H, Pott C, Rapado I, Rose SJ, Schäfer V, Touloumenidou T, Veigaard C, Venniker-Punt B, Venturi C, Vigneri P, Vorkinn I, Wilkinson E, Zadro R, Zawada M, Zizkova H, Müller MC, Saussele S, Ernst T, Machova Polakova K, Hochhaus A, Cross NCPa 62, Andreas Hochhaus 52, Nicholas C P Cross, White, He, Salmon, M, Albano, F, Andersen, Csa, Balabanov, S, Balatzenko, G, Barbany, G, Cayuela, Jm, Cerveira, N, Cochaux, P, Colomer, D, Coriu, D, Diamond, J, Dietz, C, Dulucq, S, Engvall, M, Franke, Gn, Gineikiene-Valentine, E, Gniot, M, Gómez-Casares, Mt, Gottardi, E, Hayden, C, Hayette, S, Hedblom, A, Ilea, A, Izzo, B, Jiménez-Velasco, A, Jurcek, T, Kairisto, V, Langabeer, Se, Lion, T, Meggyesi, N, Mešanović, S, Mihok, L, Mitterbauer-Hohendanner, G, Moeckel, S, Naumann, N, Nibourel, O, Oppliger Leibundgut, E, Panayiotidis, P, Podgornik, H, Pott, C, Rapado, I, Rose, Sj, Schäfer, V, Touloumenidou, T, Veigaard, C, Venniker-Punt, B, Venturi, C, Vigneri, P, Vorkinn, I, Wilkinson, E, Zadro, R, Zawada, M, Zizkova, H, Müller, Mc, Saussele, S, Ernst, T, Machova Polakova, K, Hochhaus, A, Cross NCPa, 62, Andreas Hochhaus, 52, and Nicholas C, P Cross

Subjects
Cancer Research, Cancer och onkologi, Fatigue Syndrome, Chronic, Fusion Proteins, bcr-abl, 610 Medicine & health, Hematology, Reference Standards, Treatment Outcome, Oncology, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Cancer and Oncology, Humans, Hematologi
Abstract

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.

Published
2022

9. Validation of the EuroClonality-NGS DNA capture panel as an integrated genomic tool for lymphoproliferative disorders

Author

Stewart, J, Gazdova, J, Darzentas, N, Wren, D, Proszek, P, Fazio, G, Songia, S, Alcoceba, M, Sarasquete, M, Villarese, P, Van Der Klift, M, Heezen, K, Mccafferty, N, Pal, K, Catherwood, M, Kim, C, Srivastava, S, Kroeze, L, Hodges, E, Stamatopoulos, K, Klapper, W, Genuardi, E, Ferrero, S, Van Den Brand, M, Cazzaniga, G, Davi, F, Sutton, L, Garcia-Sanz, R, Groenen, P, Macintyre, E, Bruggemann, M, Pott, C, Langerak, A, Gonzalez, D, Stewart J. P., Gazdova J., Darzentas N., Wren D., Proszek P., Fazio G., Songia S., Alcoceba M., Sarasquete M. E., Villarese P., Van Der Klift M. Y., Heezen K. C., McCafferty N., Pal K., Catherwood M., Kim C. S., Srivastava S., Kroeze L. I., Hodges E., Stamatopoulos K., Klapper W., Genuardi E., Ferrero S., Van Den Brand M., Cazzaniga G., Davi F., Sutton L. -A., Garcia-Sanz R., Groenen P. J. T. A., Macintyre E. A., Bruggemann M., Pott C., Langerak A. W., Gonzalez D., Stewart, J, Gazdova, J, Darzentas, N, Wren, D, Proszek, P, Fazio, G, Songia, S, Alcoceba, M, Sarasquete, M, Villarese, P, Van Der Klift, M, Heezen, K, Mccafferty, N, Pal, K, Catherwood, M, Kim, C, Srivastava, S, Kroeze, L, Hodges, E, Stamatopoulos, K, Klapper, W, Genuardi, E, Ferrero, S, Van Den Brand, M, Cazzaniga, G, Davi, F, Sutton, L, Garcia-Sanz, R, Groenen, P, Macintyre, E, Bruggemann, M, Pott, C, Langerak, A, Gonzalez, D, Stewart J. P., Gazdova J., Darzentas N., Wren D., Proszek P., Fazio G., Songia S., Alcoceba M., Sarasquete M. E., Villarese P., Van Der Klift M. Y., Heezen K. C., McCafferty N., Pal K., Catherwood M., Kim C. S., Srivastava S., Kroeze L. I., Hodges E., Stamatopoulos K., Klapper W., Genuardi E., Ferrero S., Van Den Brand M., Cazzaniga G., Davi F., Sutton L. -A., Garcia-Sanz R., Groenen P. J. T. A., Macintyre E. A., Bruggemann M., Pott C., Langerak A. W., and Gonzalez D.

Abstract

Current diagnostic standards for lymphoproliferative disorders include multiple tests for detection of clonal immunoglobulin (IG) and/or T-cell receptor (TCR) rearrangements, translocations, copy-number alterations (CNAs), and somatic mutations. The EuroClonality-NGS DNA Capture (EuroClonality-NDC) assay was designed as an integrated tool to characterize these alterations by capturing IGH switch regions along with variable, diversity, and joining genes of all IG and TCR loci in addition to clinically relevant genes for CNA and mutation analysis. Diagnostic performance against standard-of-care clinical testing was assessed in a cohort of 280 B-and T-cell malignancies from 10 European laboratories, including 88 formalin-fixed paraffin-embedded samples and 21 reactive lesions. DNA samples were subjected to the EuroClonality-NDC protocol in 7 EuroClonality-NGS laboratories and analyzed using a bespoke bioinformatic pipeline. The EuroClonality-NDC assay detected B-cell clonality in 191 (97%) of 197 B-cell malignancies and T-cell clonality in 71 (97%) of 73 T-cell malignancies. Limit of detection (LOD) for IG/TCR rearrangements was established at 5% using cell line blends. Chromosomal translocations were detected in 145 (95%) of 152 cases known to be positive. CNAs were validated for immunogenetic and oncogenetic regions, highlighting their novel role in confirming clonality in somatically hypermutated cases. Single-nucleotide variant LOD was determined as 4% allele frequency, and an orthogonal validation using 32 samples resulted in 98% concordance. The EuroClonality-NDC assay is a robust tool providing a single end-To-end workflow for simultaneous detection of B-and T-cell clonality, translocations, CNAs, and sequence variants.

Published
2021

16. Fludarabine in Combination with Mitoxantrone and Dexamethasone in Relapsed and Refractory Low-Grade Non-Hodgkin’s Lymphoma

Author

Pott, C., Unterhalt, M., Sandford, D. S., Markert, H., Freund, M., Engert, A., Gassmann, W., Holtkamp, W., Seufert, M., Hellriegel, K., Knauf, B., Nieberding, R., Emmerich, B., Koch, P., Wörmann, B., Hiddemann, W., Hiddemann, W., editor, Plunkett, W., editor, Büchner, T., editor, Ritter, J., editor, Wörmann, B., editor, Keating, M. J., editor, and Creutzig, U., editor

Published
1996
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20. Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS

Author

Knecht, H, Reigl, T, Kotrova, M, Appelt, F, Stewart, P, Bystry, V, Krejci, A, Grioni, A, Pal, K, Stranska, K, Plevova, K, Rijntjes, J, Songia, S, Svaton, M, Fronkova, E, Bartram, J, Scheijen, B, Herrmann, D, Garcia-Sanz, R, Hancock, J, Moppett, J, van Dongen, J, Cazzaniga, G, Davi, F, Groenen, P, Hummel, M, Macintyre, E, Stamatopoulos, K, Trka, J, Langerak, A, Gonzalez, D, Pott, C, Bruggemann, M, Darzentas, N, Knecht H., Reigl T., Kotrova M., Appelt F., Stewart P., Bystry V., Krejci A., Grioni A., Pal K., Stranska K., Plevova K., Rijntjes J., Songia S., Svaton M., Fronkova E., Bartram J., Scheijen B., Herrmann D., Garcia-Sanz R., Hancock J., Moppett J., van Dongen J. J. M., Cazzaniga G., Davi F., Groenen P. J. T. A., Hummel M., Macintyre E. A., Stamatopoulos K., Trka J., Langerak A. W., Gonzalez D., Pott C., Bruggemann M., Darzentas N., Knecht, H, Reigl, T, Kotrova, M, Appelt, F, Stewart, P, Bystry, V, Krejci, A, Grioni, A, Pal, K, Stranska, K, Plevova, K, Rijntjes, J, Songia, S, Svaton, M, Fronkova, E, Bartram, J, Scheijen, B, Herrmann, D, Garcia-Sanz, R, Hancock, J, Moppett, J, van Dongen, J, Cazzaniga, G, Davi, F, Groenen, P, Hummel, M, Macintyre, E, Stamatopoulos, K, Trka, J, Langerak, A, Gonzalez, D, Pott, C, Bruggemann, M, Darzentas, N, Knecht H., Reigl T., Kotrova M., Appelt F., Stewart P., Bystry V., Krejci A., Grioni A., Pal K., Stranska K., Plevova K., Rijntjes J., Songia S., Svaton M., Fronkova E., Bartram J., Scheijen B., Herrmann D., Garcia-Sanz R., Hancock J., Moppett J., van Dongen J. J. M., Cazzaniga G., Davi F., Groenen P. J. T. A., Hummel M., Macintyre E. A., Stamatopoulos K., Trka J., Langerak A. W., Gonzalez D., Pott C., Bruggemann M., and Darzentas N.

Abstract

Assessment of clonality, marker identification and measurement of minimal residual disease (MRD) of immunoglobulin (IG) and T cell receptor (TR) gene rearrangements in lymphoid neoplasms using next-generation sequencing (NGS) is currently under intensive development for use in clinical diagnostics. So far, however, there is a lack of suitable quality control (QC) options with regard to standardisation and quality metrics to ensure robust clinical application of such approaches. The EuroClonality-NGS Working Group has therefore established two types of QCs to accompany the NGS-based IG/TR assays. First, a central polytarget QC (cPT-QC) is used to monitor the primer performance of each of the EuroClonality multiplex NGS assays; second, a standardised human cell line-based DNA control is spiked into each patient DNA sample to work as a central in-tube QC and calibrator for MRD quantification (cIT-QC). Having integrated those two reference standards in the ARResT/Interrogate bioinformatic platform, EuroClonality-NGS provides a complete protocol for standardised IG/TR gene rearrangement analysis by NGS with high reproducibility, accuracy and precision for valid marker identification and quantification in diagnostics of lymphoid malignancies.

Published
2019

21. Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study

Author

Bruggemann, M, Kotrova, M, Knecht, H, Bartram, J, Boudjogrha, M, Bystry, V, Fazio, G, Fronkova, E, Giraud, M, Grioni, A, Hancock, J, Herrmann, D, Jimenez, C, Krejci, A, Moppett, J, Reigl, T, Salson, M, Scheijen, B, Schwarz, M, Songia, S, Svaton, M, van Dongen, J, Villarese, P, Wakeman, S, Wright, G, Cazzaniga, G, Davi, F, Garcia-Sanz, R, Gonzalez, D, Groenen, P, Hummel, M, Macintyre, E, Stamatopoulos, K, Pott, C, Trka, J, Darzentas, N, Langerak, A, Bruggemann M., Kotrova M., Knecht H., Bartram J., Boudjogrha M., Bystry V., Fazio G., Fronkova E., Giraud M., Grioni A., Hancock J., Herrmann D., Jimenez C., Krejci A., Moppett J., Reigl T., Salson M., Scheijen B., Schwarz M., Songia S., Svaton M., van Dongen J. J. M., Villarese P., Wakeman S., Wright G., Cazzaniga G., Davi F., Garcia-Sanz R., Gonzalez D., Groenen P. J. T. A., Hummel M., Macintyre E. A., Stamatopoulos K., Pott C., Trka J., Darzentas N., Langerak A. W., Bruggemann, M, Kotrova, M, Knecht, H, Bartram, J, Boudjogrha, M, Bystry, V, Fazio, G, Fronkova, E, Giraud, M, Grioni, A, Hancock, J, Herrmann, D, Jimenez, C, Krejci, A, Moppett, J, Reigl, T, Salson, M, Scheijen, B, Schwarz, M, Songia, S, Svaton, M, van Dongen, J, Villarese, P, Wakeman, S, Wright, G, Cazzaniga, G, Davi, F, Garcia-Sanz, R, Gonzalez, D, Groenen, P, Hummel, M, Macintyre, E, Stamatopoulos, K, Pott, C, Trka, J, Darzentas, N, Langerak, A, Bruggemann M., Kotrova M., Knecht H., Bartram J., Boudjogrha M., Bystry V., Fazio G., Fronkova E., Giraud M., Grioni A., Hancock J., Herrmann D., Jimenez C., Krejci A., Moppett J., Reigl T., Salson M., Scheijen B., Schwarz M., Songia S., Svaton M., van Dongen J. J. M., Villarese P., Wakeman S., Wright G., Cazzaniga G., Davi F., Garcia-Sanz R., Gonzalez D., Groenen P. J. T. A., Hummel M., Macintyre E. A., Stamatopoulos K., Pott C., Trka J., Darzentas N., and Langerak A. W.

Abstract

Amplicon-based next-generation sequencing (NGS) of immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements for clonality assessment, marker identification and quantification of minimal residual disease (MRD) in lymphoid neoplasms has been the focus of intense research, development and application. However, standardization and validation in a scientifically controlled multicentre setting is still lacking. Therefore, IG/TR assay development and design, including bioinformatics, was performed within the EuroClonality-NGS working group and validated for MRD marker identification in acute lymphoblastic leukaemia (ALL). Five EuroMRD ALL reference laboratories performed IG/TR NGS in 50 diagnostic ALL samples, and compared results with those generated through routine IG/TR Sanger sequencing. A central polytarget quality control (cPT-QC) was used to monitor primer performance, and a central in-tube quality control (cIT-QC) was spiked into each sample as a library-specific quality control and calibrator. NGS identified 259 (average 5.2/sample, range 0–14) clonal sequences vs. Sanger-sequencing 248 (average 5.0/sample, range 0–14). NGS primers covered possible IG/TR rearrangement types more completely compared with local multiplex PCR sets and enabled sequencing of bi-allelic rearrangements and weak PCR products. The cPT-QC showed high reproducibility across all laboratories. These validated and reproducible quality-controlled EuroClonality-NGS assays can be used for standardized NGS-based identification of IG/TR markers in lymphoid malignancies.

Published
2019

23. The Rhaetian flora of Wüstenwelsberg, Bavaria, Germany: Description of selected gymnosperms (Ginkgoales, Cycadales, Coniferales) together with an ecological assessment of the locally prevailing vegetation

Author

van Konijnenburg - van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., Kustatscher, E., Marine palynology and palaeoceanography, Marine Palynology, Marine palynology and palaeoceanography, and Marine Palynology

Subjects
0106 biological sciences, 010506 paleontology, Flora, Evolution, Range (biology), 010603 evolutionary biology, 01 natural sciences, Behavior and Systematics, Genus, Abundance (ecology), Cycad, Ginkgoites, Late Triassic, Ecology, Evolution, Behavior and Systematics, 0105 earth and related environmental sciences, Ecology, biology, Palaeontology, Paleontology, Vegetation, biology.organism_classification, Cretaceous, Conifers, Franconia, Becklesia, Geography, Paleoecology
Abstract

This paper describes the ginkgoaleans (Ginkgoites) and conifers (Palissya, Stachyotaxus, Schizolepis) of the Rhaetian flora from Wustenwelsberg, as well as a new species of the cycad Becklesia. The ginkgophyte leaf fragments are very abundant in certain levels (‘Blatterkohle‘) whereas conifers are common in the main fossiliferous bed. The Wustenwelsberg specimens extend the range for Ginkgoites taeniatus from the Hettangian to the Rhaetian and for the genus Becklesia from the Cretaceous to the Rhaetian. The other elements are typical for the Rhaetian floras of Bavaria and often also of the Northern Hemisphere. A comparison with other Northern Hemisphere plant assemblages demonstrates a high similarity with the Rhaetian floras from Jameson Land (Greenland) and Scania (Sweden) but significant differences to the Hettangian floras from adjacent areas in Franconia, especially at species and sometimes at generic level. A comparison with the microflora from the same sections shows a hidden diversity that is highest in small herbaceous plants (mosses, lycophytes, ferns) and in the conifers. Wustenwelsberg reflects, thus, an articulated landscape with a high water and nutrients availability (stagnant water bodies and/or river systems) covered by a complex and multi-storeyed vegetation shown, among others, by the general abundance in hygrophytic spores and high diversity among the various plant groups. This must have corresponded to one of the humid episodes that characterized the generally warm and arid climate of the Rhaetian of Europe.

Published
2021

24. PREDICTION OF RELAPSE BY STANDARDIZED IG‐BASED ALLEL‐SPECIFIC QPCR, DDPCR AND AMPLICON NGS FOR MRD MONITORING IN MANTLE CELL LYMPHOMA: A COMPARATIVE ANALYSIS BY THE EU‐MCL NETWORK

Author

Pott, C., primary, Macintyre, E., additional, Delfau, M.‐H., additional, Weiß, A., additional, Schilhabel, A., additional, Soehlbrand, A., additional, Kehden, B., additional, Darzentas, N., additional, Kotrova, M., additional, Schoen, F., additional, Ribrag, V., additional, Brueggemann, M., additional, Villarese, P., additional, Dreyling, M., additional, Hermine, O., additional, Kluin‐Nelemans, H., additional, Jiang, L., additional, and Hoster, E., additional

Published
2021
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25. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

Author

Agathangelidis, A. Chatzidimitriou, A. Gemenetzi, K. Giudicelli, V. Karypidou, M. Plevova, K. Davis, Z. Yan, X.-J. Jeromin, S. Schneider, C. Pedersen, L.B. Tschumper, R.C. Sutton, L.-A. Baliakas, P. Scarfò, L. van Gastel, E.J. Armand, M. Tausch, E. Biderman, B. Baer, C. Bagnara, D. Navarro, A. Langlois de Septenville, A. Guido, V. Mitterbauer-Hohendanner, G. Dimovski, A. Brieghel, C. Lawless, S. Meggendorfer, M. Brazdilova, K. Ritgen, M. Facco, M. Tresoldi, C. Visentin, A. Patriarca, A. Catherwood, M. Bonello, L. Sudarikov, A. Vanura, K. Roumelioti, M. Skuhrova Francova, H. Moysiadis, T. Veronese, S. Giannopoulos, K. Mansouri, L. Karan-Djurasevic, T. Sandaltzopoulos, R. Bödör, C. Fais, F. Kater, A. Panovska, I. Rossi, D. Alshemmari, S. Panagiotidis, P. Costeas, P. Espinet, B. Antic, D. Foroni, L. Montillo, M. Trentin, L. Stavroyianni, N. Gaidano, G. Francia di Celle, P. Niemann, C. Campo, E. Anagnostopoulos, A. Pott, C. Fischer, K. Hallek, M. Oscier, D. Stilgenbauer, S. Haferlach, C. Jelinek, D. Chiorazzi, N. Pospisilova, S. Lefranc, M.-P. Kossida, S. Langerak, A.W. Belessi, C. Davi, F. Rosenquist, R. Ghia, P. Stamatopoulos, K. ERIC, the European Research Initiative on CLL

Subjects
hemic and lymphatic diseases
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed “satellites,” were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL. Key Points: • In a series of 29 856 CLL patients, the incidence of BcR stereotypy peaked at 41%. • Higher-order relations exist between stereotyped subsets, particularly for those from U-CLL, for which satellite subsets were identified. © 2021 American Society of Hematology

Published
2021

26. The Rhaetian flora of Wüstenwelsberg, Bavaria, Germany: Description of selected gymnosperms (Ginkgoales, Cycadales, Coniferales) together with an ecological assessment of the locally prevailing vegetation

Author

Marine palynology and palaeoceanography, Marine Palynology, van Konijnenburg - van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., Kustatscher, E., Marine palynology and palaeoceanography, Marine Palynology, van Konijnenburg - van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., and Kustatscher, E.

Published
2021

30. EKG-Quiz

Author

Bauersachs, J., Borggrefe, M., Eckardt, L., Ehlermann, P., Engberding, R., Frommeyer, G., Fabritz, L., Friedrich, C., Gerecke, B., Herrera-Siklody, C., Katus, H. A., Kirchhof, P., McKenna, W. J., Oswald, H., Paul, M., Parade, U., Pott, C., Rüb, N., Schimpf, R., Seebohm, G., Schulze-Bahr, E., Sen-Chowdhry, Srijita, Stallmeyer, B., Strotmann, C., Tomé Esteban, M. T., Veltmann, C., Waltenberger, J., Wichter, T., Wolpert, C., and Zumhagen, S.

Published
2012
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37. Ferns and fern allies in the Rhaetian flora of Wüstenwelsberg, Bavaria, Germany

Author

van Konijnenburg-van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., Kustatscher, E., van Konijnenburg-van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., and Kustatscher, E.

Abstract

The Rhaetian flora from Wüstenwelsberg (Franconia, southern Germany) comprises a diverse array of cryptogam plants. Twelve species of lycophytes, sphenophytes and ferns are identified and described by means of macromorphology and in situ spores, when present. The study is part of the ongoing examination of this recently excavated and excellently preserved fossil plant assemblage. In total, two lycophyte taxa (Lepacyclotes and Selaginellites) and one sphenophyte (Equisetites) have been identified. Ferns are represented by eight species in three families; Osmundaceae with one Todites and two Cladophlebis species; Matoniaceae with two Phlebopteris species, and Dipteridaceae with Clathropteris, Dictyophyllum and Thaumatopteris with one species each. Curled fern fronds have been attributed to the fossil-genus Spiropteris. Besides several key Rhaetian taxa, two key taxa for Hettangian floras, Phlebopteris angustiloba and Thaumatopteris brauniana, are present in Wüstenwelsberg, albeit not in large numbers. The comparison of the flora from Wüstenwelsberg with adjacent Rhaetian floras revealed distinct local differences in the respective floras, which are discussed in the light of paleogeography involving dispersal patterns or mechanisms and adaptations of the plants.

Published
2020

38. Ferns and fern allies in the Rhaetian flora of Wüstenwelsberg, Bavaria, Germany

Author

Marine palynology and palaeoceanography, Marine Palynology, van Konijnenburg-van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., Kustatscher, E., Marine palynology and palaeoceanography, Marine Palynology, van Konijnenburg-van Cittert, J.H.A., Pott, C., Schmeißner, S., Dütsch, G., and Kustatscher, E.

Published
2020

42. Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia

Author

Hofmann, W., Seipelt, G., Langenhan, S., Reutzel, R., Schott, D., Schoeffski, O., Illiger, H., Hartmann, F., Balleisen, L., Franke, A., Fiedler, F., Huber, C., Rasche, H., Bergmann, L., Ganser, A., Pott, C., Pasold, R., Rudolph, C., Ottmann, O., Gökbuget, N., and Hoelzer, D.

Published
2002
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44. Sequencing of pediatric Burkitt lymphoma within the ICGC MMML-Seq project: 12

Author

Richter, J, Schlesner, M, Leich, E, Burkhardt, B, Hoffmann, S, Szczepanowski, M, Kreuz, M, Lenze, D, Bernhart, S, Rosolowski, M, Hoell, J, Lawerenz, C, Jâger, N, Hutter, B, Langerberger, D, Ammerpohl, O, Binder, H, Borkhardt, A, Brors, B, Claviez, A, Pischimarov, J, Dreyling, M, Eils, R, Hansmann, M-L, Binder, V, Hornig, N, Klapper, W, Korbel, J, Kube, D, Kûppers, R, Lichter, P, Loeffler, M, Môller, P, Pott, C, Rosenwald, A, Schreiber, Sefan, Schilhabel, M, Scholtysik, R, Stadler, P F, Trautmann, H, Wagener, R, Zenz, T, Trûmper, L, Rosenstiel, P, Hummel, M, and Siebert, R

Published
2012

46. Minimal residual disease (MRD) is a predictor of clinical outcome in elderly patients with MCL and identifies patients with long lasting remissions after R-CHOP or R-FC induction followed by maintenance with rituximab or IFN: first results of the randomized EU-MCL elderly trial: V115

Author

Pott, C., Delfau-Larue, M.-H., Beldjord, K., Böttcher, S., Macintyre, E., Asnafi, V., Siebert, R., Klapper, W., Unterhalt, M., Kneba, M., Hiddemann, W., Hermine, O., Kluin-Nelemans, H., Dreyling, M., and Hoster, E.

Published
2011

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