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

Author

Jos Rijntjes, K. Stamatopoulos, C. Pott, Ramón García-Sanz, Karla Plevová, Giovanni Cazzaniga, Elizabeth Macintyre, Nikos Darzentas, Blanca Scheijen, John Moppett, F. Appelt, Jack Bartram, Eva Froňková, Michael Svatoň, Frederic Davi, Michaela Kotrova, Jan Trka, Simona Songia, Kamila Stránská, Andrea Grioni, Henrik Knecht, Monika Brüggemann, David Gonzalez, Dietrich Herrmann, Michael Hummel, Karol Pál, Anthonie Willem Langerak, Tomáš Reigl, Adam Krejci, van Dongen Jjm, Groenen Pjta, J. Hancock, Peter Stewart, Bystry, Immunology, Ministry of Health of the Czech Republic, Associazione Italiana per la Ricerca sul Cancro, 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, and Darzentas, N

Subjects
0301 basic medicine, Genetic Markers, Quality Control, Cancer Research, Neoplasm, Residual, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Receptors, Antigen, T-Cell, Immunoglobulins, Human cell line, Computational biology, Biology, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], DNA sequencing, Article, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Genetic Marker, Genetics research, Immunoglobulin, Humans, Multiplex, Cancer genetics, Gene Rearrangement, Computational Biology, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Hematology, Gene rearrangement, Minimal residual disease, 3. Good health, Identification (information), 030104 developmental biology, Oncology, Genetic marker, 030220 oncology & carcinogenesis, Primer (molecular biology), Human
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., This work was supported by Ministry of Health of the Czech Republic, grant no. 16-34272A; computational resources were provided by the CESNET LM2015042 and the CERIT Scientific Cloud LM2015085, provided under the programme “Projects of Large Research, Development, and Innovations Infrastructures”. Analyses in Prague (JT, EF and MS) were supported by Ministry of Health, Czech Republic, grant no. 00064203, and by PRIMUS/17/MED/11. Analyses in the Monza (Centro Ricerca Tettamanti, SS, AG and GC) laboratory were supported by the Italian Association for Cancer Research (AIRC) and Comitato Maria Letizia Verga.

Published
2019

2. COMPARATIVE EVALUATION OF CD229, CD319 AND CD54 FOR FLOW CYTOMETRIC IDENTIFICATION OF BONE MARROW NORMAL/REACTIVE AND CLONAL/ABERRANT PLASMA CELLS

Author

Sanoja Flores, L, Flores Montero, J, Puig, N, Pérez Morán, J, Paiva, B, Vidriales, MB, Fernández Roldán, MC, Mateos, MV, van Dongen, JJM, Orfao A., POJERO, Fanny, Sanoja Flores, L, Pojero, F, Flores-Montero, J, Puig, N, Pérez-Morán, J, Paiva, B, Vidriales, MB, Fernández-Roldán, MC, Mateos, MV, van Dongen, JJM, and Orfao A

Subjects
FLOW CYTOMETRY, MULTIPLE MYELOMA
Published
2014

3. Strategieën Voor Repertoire Analyse

Author

Ijspeert, Hanna, Schouwenburg, Pauline, van der Burg, Mirjam, van Dongen, JJM, Brooimans, RA, Dik, WA, langerak, AW, Schreurs, MWJ, van der Velden, VHJ, and Immunology

Published
2016

5. Graves' orbitopathie: pathogenese en behandeling

Author

Dik, Wim, Paridaens, D, Dalm, V.A.S.H., Peeters, Robin, van Hagen, P.M., van Dongen, JJM, Brooimans, RA, Dik, WA, Langerak, AW, Schreurs, MWJ, van der Velden, VHJ, Immunology, and Internal Medicine

Published
2016

7. T-Cel Deficiënties

Author

van der Burg, Mirjam, Ijspeert, Hanna, Driessen, Gertjan, van Dongen, JJM, Brooimans, RA, Langerak, AW, Schreurs, MWJ, van der Velden, VHJ, Immunology, and Pediatrics

Published
2016

8. Standardized Next-Generation Flow Cytometry for Highly Sensitive Mrd Measurements in B-Cell Acute Lymphoblastic Leukemia

Author

Theunissen, Prisca, Mejstrikova, E, Sedek, L, van der Sluijs, A, Gaipa, G, Bartels, M, Sobral de Costa, E, Kotrova, M, Novakova, M, Sonneveld, E, Baracchi, C, Bonaccorso, P, Oliviera, E, te Marvelde, Jeroen, Szczepanski, Tomek, Lhermitte, L, Hrusak, O, Lecrevisse, Q, Grigore, GE, Fronkova, E, Trka, J, Bruggemann, M, Orfao, A, Dongen, Jacques, van der Velden, Vincent, van Dongen, JJM, Immunology, and Plastic and Reconstructive Surgery and Hand Surgery

Published
2016

12. Ziekte van Behçet

Author

van Laar, Jan, van Hagen, P.M., Kappen, Jasper, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, and Internal Medicine

Published
2010

13. Inleiding leukemieën en lymfomen

Author

van der Velden, Vincent, Langerak, Ton, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

16. Het EuroFlow programma

Author

Dongen, Jacques, Orfao, A, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

17. Multipele sclerose

Author

Laman, Jon, Hintzen, Rogier, Hart, Boris, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, and Neurology

Published
2010

18. Flowcytometrische analyse van 'small samples'

Author

Langerak, Ton, Tielemans, Dennis, Missotten, TOAR, Baarsma, GS, Vermeulen, Joyce, van der Spek, Ashley, Martin-Martin, L, Almeida, J, Flores-Montero, J, Cullen, M, Mejstrikova, E, Wind, Henk, van der Velden, Vincent, Orfao, A, Dongen, Jacques, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, Internal Medicine, and Ophthalmology

Published
2010

20. Het syndroom van Sjögren

Author

Versnel, Marjan, Brkic, Zana, Van Helden - Meeuwsen, Corine, Merwe, Joop, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

23. Diagnosis and classification of acute lymphoblastic leukemia

Author

Lhermitte, L, Asnafi, V, Flores-Montero, J, Lecrevisse, Q, Sedek, L, Szczepanski, Tomek, Bottcher, S, Bruggemann, M, Mejstrikova, E, Kalina, T, De Mendonca, A, Lucio, P, Cullen, M, Richards, S, te Marvelde, Jeroen, Wind, Henk, van der Velden, Vincent, van der Sluijs, AJ, Vidriales, MB, Hernandez, J, Costa, ES, Macintyre, E, Dongen, Jacques, Orfao, A, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

25. Histiocytaire syndromen

Author

Leenen, Pieter, van Laar, Jan, Egeler, RM, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, and Pediatrics

Published
2010

26. Diagnosis and classification of mature B-cell malignancies

Author

Bottcher, S, Rawstron, AC, Lucio, P, Macintyre, E, Lima, M, van der Velden, Vincent, Dongen, Jacques, Orfao, A, Kneba, M, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

29. Detectie van cytokinen in de diagnostiek van ontstekingsprocessen

Author

Dik, Wim, van Laar, Jan, Nijenhuis, Marja, Couwenberg, Marion, Nagtzaam, Nicole, Bastiaans, Jeroen, Kamphuis, L, Kuijpers, Robert, Hooijkaas, H (Herbert), van Hagen, P.M., van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, and Ophthalmology

Published
2010

31. De monocyt als potentieel diagnosticum

Author

Drexhage, Hemmo, Drexhage, Roosmarijn, Nieuwenhuijsen, Leonie, Padmos, Roos, Weigelt, Karin, Beumer, Wouter, Bergink, Veerle, Burgerhout, Karin, Knijff, EM (Esther), Versnel, Marjan, Leenen, Pieter, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, Immunology, Cell biology, and Psychiatry

Published
2010

32. Inleiding primaire immunodeficiënties

Author

Dongen, Jacques, van der Burg, Mirjam, van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

33. Inleiding auto-immuunziekten

Author

Hooijkaas, H (Herbert), van Dongen, JJM, Dik, WA, Langerak, AW, van der Velden, VHJ, Hooijkaas, H, and Immunology

Published
2010

37. Flowcytometrische screening voor het HLA-B27 antigen

Author

Levering, WHBM, Wind, Henk, Sintnicolaas, K, Hooijkaas, H (Herbert), Gratama, JW (S.), Loghem, EG, van der Velden, VHJ, Hooijkaas, H., van Dongen, JJM, Immunology, and Medical Oncology

Published
2003

40. Precursor-B-ALL with D-H-J(H) gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14

Author

Szczepanski, T, Willemse, MJ, van Wering, ER, van Weerden, J.F., Kamps, WA, and van Dongen, JJM

Subjects
precursor-B-ALL, IMMUNOGLOBULIN HEAVY-CHAIN, D-H-J(H) gene rearrangements, IGH gene, CHILDHOOD, DIVERSITY, MINIMAL RESIDUAL DISEASE, TIME QUANTITATIVE PCR, CLONAL REARRANGEMENTS, SOUTHERN BLOT ANALYSIS, children, CELL RECEPTOR GENES, HUMAN BONE-MARROW, ACUTE LYMPHOBLASTIC-LEUKEMIA
Abstract

The IGH gene configuration was investigated in 97 childhood precursor-B-ALL patients at initial diagnosis. Rearrangements were found by Southern blotting in all but three patients (97%) and in 30 cases (31%) we observed oligoclonal IGH gene rearrangements. Heteroduplex PCR analysis revealed at least one clonal PCR product in all Southern blot-positive cases. In 89 patients (92%) complete V(D)J rearrangements were found, while incomplete D-H-J(H) rearrangements occurred in only 21 patients (22%). In 5% of cases the DH-JH rearrangements were the sole IGH gene rearrangements. Sequence analysis of the 31 identified incomplete rearrangements revealed preferential usage of segments from the D(H)2, D(H)3 and D(H)7 families (78%). While D(H)2 and D(H)3 gene rearrangements occur frequently in normal B cells and B cell precursors, the relatively frequent usage of D(H)7-27 (19%) in precursor-B-ALL patients is suggestive of leukemic transformation during prenatal lymphopoiesis. Among J(H) gene segments in the incomplete DH-JH rearrangements, the J(H)6 segment was significantly overrepresented (61%). This observation together with the predominant usage of the most upstream D-H genes indicates that many of the identified clonal D-H-J(H) gene rearrangements in precursor-B-ALL probably represent secondary recombinations, having deleted pre-existing D-H-J(H) joinings. The patients with incomplete D-H-J(H) gene rearrangements were frequently characterized by hyperdiploid karyotype with additional copies of chromosome 14 and/or by IGH oligoclonality. The presence of incomplete D-H-J(H) joinings was also significantly associated with a less mature immunogenotype: overrepresentation Of V(H)6-1 gene segment usage, absence of biallelic TCRD deletions, and low frequency of TCRG gene rearrangements. This immature immunogenotype of precursor-B-ALL with incomplete IGH gene rearrangements was not associated with more aggressive disease.

Published
2001

41. SIHONSCORE: a scoring system for external quality control of leukaemia/lymphoma immunophenotyping measuring all analytical phases of laboratory performance

Author

Kluin-Nelemans, JC, van Wering, ER, van der Schoot, CE, Adriaansen, HJ, van't Veer, MB, van Dongen, JJM, Gratama, JW, University of Groningen, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
immunophenotyping, leukaemia, FLOW-CYTOMETRY, LYMPHOMA, LEUKEMIA, external quality control, CLASSIFICATION
Abstract

For the diagnosis of leukaemia and leukaemic lymphoma, clinicians frequently have to rely on the results of immunophenotyping. To improve the quality of these results, the Dutch Foundation for Immunophenotyping of Haematological Malignancies (SIHON) initiated external quality rounds in 1986. Over a period of more than 10 years, this has led to improvements in the interpretation of immunophenotyping results. However, the evaluation of results focused mainly on the correctness of the interpretation of the immunophenotypical data, leaving the preceding analytical phases unevaluated. Therefore, in 1996 SIHON developed a more comprehensive scoring system, called SIHONSCORE, covering all three phases of immunophenotyping, namely the pre-analytical (i.e. choice of the staining panels), analytical (i.e. the technical part consisting of sample preparation, data acquisition and analysis) and the post-analytical phase (i.e. the interpretation) of the laboratory process. Here, we report how SIHONSCORE was successfully applied to three consecutive external quality rounds consisting of a total of nine different cases tested. For laboratory certification, participation in external quality control programmes is required. Evidently, criteria are needed to define the minimum acceptable performance of a certified laboratory. With SIHONSCORE, a useful instrument is obtained evaluating all phases of the performance of laboratories in leukaemia and lymphoma immunophenotyping.

Published
2001

42. Two consecutive immunophenotypic switches in a child with immunogenotypically stable acute leukaemia

Author

Bierings, M, Szczepanski, T, van Wering, ER, Willemse, MJ, Langerak, AW, Revesz, T, van Dongen, JJM, Immunology, and University of Groningen

Subjects
acute leukaemia, EXPRESSION, phenotypic switch, MINIMAL RESIDUAL DISEASE, PCR TARGETS, precursor B-ALL, DIAGNOSIS, SOUTHERN BLOT ANALYSIS, BIPHENOTYPIC LEUKEMIA, AML, hemic and lymphatic diseases, stable immunogenotype, IMMUNOGLOBULIN, CELL RECEPTOR GENES, ACUTE LYMPHOBLASTIC-LEUKEMIA, REARRANGEMENT PATTERNS
Abstract

A 12-year-old girl presented with a CD33(+) precursor B-acute lymphoblastic leukaemia (ALL) and seemed to respond well to ALL treatment. However. 2 weeks after diagnosis her leucocyte count rose rapidly with a predominance of myeloid blasts with M5b morphology and CD19(+) myeloid immunophenotype. Acute myeloid leukaemia (AML) treatment was started and remission was achieved after one course of chemotherapy; the AML treatment was continued for 6 months. Two months after cessation of chemotherapy, the patient developed a bone marrow relapse, this time with an undifferentiated blast morphology and a precursor B immunophenotype. Molecular analysis of the immunoglobulin and T-cell receptor genes showed several clonal gene rearrangements at diagnosis: two IGH, two IGK and two TCRD gene rearrangements. All rearrangements were also detected during the AML phase of the disease, suggesting a phenotypic shift of the same leukaemia. At relapse, 8 months later, all rearrangements were preserved except for one TCRD (V delta2-D delta3) rearrangement. The first phenotypic shift in the genotypically stable leukaemia was remarkably fast. The most probable explanation for our observations is an oncogenic event in an undifferentiated haematopoetic progenitor clone, with a highly versatile phenotype.

Published
2001

43. Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: implications for monitoring of minimal residual disease

Author

van Wering, ER, Van der Linden-Schrever, BEM, Szczepanski, T, Willemse, MJ, Baars, EA, Van Wijngaarde-Schmitz, HM, Kamps, WA, Van Dongen, JJM, Immunology, and Faculteit Medische Wetenschappen/UMCG

Subjects
B-cell precursors, LYMPHOID-CELLS, FLOW CYTOMETRIC ANALYSIS, PEDIATRIC BONE-MARROW, POSITIVE CELLS, RECEPTOR GENE REARRANGEMENTS, CHILDREN, PCR TARGETS, PERIPHERAL-BLOOD, regenerating bone marrow, AGE-RELATED-CHANGES, immunophenotyping, hemic and lymphatic diseases, minimal residual disease, ACUTE-LEUKEMIA, ALL
Abstract

We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) and 600 blood samples] by use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10 and CD19. Additionally 60 BM follow-up samples from six patients were subjected to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions of normal precursor B cells in regenerating BM not only after maintenance therapy but also during treatment. At the end of the 2-week intervals after consolidation and reinduction treatment, B-cell-lineage regeneration was observed in BM with a large fraction of immature CD34(+)/TdT(+) B cells. In contrast, in regenerating BM after cessation of maintenance treatment, the more mature CD19(+)/CD10(+) B cells were significantly increased, but the fraction of immature CD34(+)/TdT(+) B cells was essentially smaller. Blood samples showed a profound B-cell lymphopenia during treatment followed by a rapid normalization of blood B cells after treatment, with a substantial CD10(+) fraction (10-30%). Heteroduplex PCR analysis confirmed the polyclonal origin of the expanded precursor B cells in regenerating BM. This information regarding the regeneration of BM is essential for the correct interpretation of minimal residual disease studies.

Published
2000

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