50 results on '"Cauwelier, B."'
Search Results
2. Parvovirus B19-triggered hemophagocytic lymphohistiocytosis in a patient with Crohn’s disease
- Author
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Debels, L, primary, Reynders, M, additional, Cauwelier, B, additional, Willandt, B, additional, Selleslag, D, additional, and Snauwaert, C, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Evaluation of schistocyte analysis by a novel automated digital cell morphology application
- Author
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HERVENT, A.-S., GODEFROID, M., CAUWELIER, B., BILLIET, J., and EMMERECHTS, J.
- Published
- 2015
- Full Text
- View/download PDF
4. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique
- Author
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Cauwelier, B, Cavé, H, Gervais, C, Lessard, M, Barin, C, Perot, C, Van den Akker, J, Mugneret, F, Charrin, C, Pagès, M P, Grégoire, M-J, Jonveaux, P, Lafage-Pochitaloff, M, Mozzicconacci, M J, Terré, C, Luquet, I, Cornillet-Lefebvre, P, Laurence, B, Plessis, G, Lefebvre, C, Leroux, D, Antoine-Poirel, H, Graux, C, Mauvieux, L, Heimann, P, Chalas, C, Clappier, E, Verhasselt, B, Benoit, Y, Moerloose, B D, Poppe, B, Van Roy, N, Keersmaecker, K D, Cools, J, Sigaux, F, Soulier, J, Hagemeijer, A, Paepe, A D, Dastugue, N, Berger, R, and Speleman, F
- Published
- 2007
- Full Text
- View/download PDF
5. Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRβ locus rearrangements and putative new T-cell oncogenes
- Author
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Cauwelier, B, Dastugue, N, Cools, J, Poppe, B, Herens, C, De Paepe, A, Hagemeijer, A, and Speleman, F
- Published
- 2006
- Full Text
- View/download PDF
6. HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation
- Author
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Bergeron, J, Clappier, E, Cauwelier, B, Dastugue, N, Millien, C, Delabesse, E, Beldjord, K, Speleman, F, Soulier, J, Macintyre, E, and Asnafi, V
- Published
- 2006
- Full Text
- View/download PDF
7. A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias
- Author
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Speleman, F, Cauwelier, B, Dastugue, N, Cools, J, Verhasselt, B, Poppe, B, Van Roy, N, Vandesompele, J, Graux, C, Uyttebroeck, A, Boogaerts, M, De Moerloose, B, Benoit, Y, Selleslag, D, Billiet, J, Robert, A, Huguet, F, Vandenberghe, P, De Paepe, A, Marynen, P, and Hagemeijer, A
- Published
- 2005
- Full Text
- View/download PDF
8. Evaluation of a disk diffusion method with cefoxitin (30 μg) for detection of methicillin-resistant Staphylococcus aureus
- Author
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Cauwelier, B., Gordts, B., Descheemaecker, P., and Van Landuyt, H.
- Published
- 2004
- Full Text
- View/download PDF
9. A NEW RECURRENT INVERSION, INV(7) LEADS TO TRANSCRIPTIONAL ACTIVATION OF HOXA10 AND HOXA11 IN A SUBSET OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: P.S.002
- Author
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Cauwelier, B., Speleman, Frank, Dastugue, Nicole, Cools, Jan, Verhasselt, Bruno, Poppe, Bruce, Van roy, nadine, vadesompele, Jo, graux, Carlos, Uyttebroeck, anne, Boogaerts, Marc, De Moerloose, Barbara, Benoit, Yves, Selleslag, Dominik, Billiet, Johan, Vandenberghe, Peter, De Paepe, Anne, marynen, Peter, and Hagemeijer, Anne
- Published
- 2005
10. A novel approach for BCR-ABL1 standardization to improve International Scale estimation
- Author
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Maes, B, Bakkus, M, Boeckx, N, Boone, E, Cauwelier, B, Denys, B, De Schouwer, P, Devos, T, El Housni, H, Hillen, F, Jacobs, K, Lambert, F, Louagie, H, Maes, M-B, Meeus, P, Moreau, E, Nollet, F, Peeters, K, Saussoy, P, Van Lint, P, Vaerman, J-L, Vaeyens, F, Vandepoele, K, Vannuffel, P, Ver Elst, K, Vermeulen, K, Bruyndonckx, R, Belgian working group on BCR-ABL1 IS standardization, Amsterdam Movement Sciences, Rehabilitation medicine, Hematology, and Belgian Working Grp BCR-ABL1 IS St
- Subjects
Standardization ,Process (engineering) ,International scale ,Clinical Biochemistry ,Fusion Proteins, bcr-abl ,methods ,03 medical and health sciences ,Bcr abl1 ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,External quality assessment ,Medicine ,Genetic Testing ,RNA, Messenger ,Retrospective Studies ,Estimation ,Observer Variation ,SIMPLE (military communications protocol) ,business.industry ,international cooperation ,Biochemistry (medical) ,Conversion factor ,Hematology ,General Medicine ,Reference Standards ,chronic myelogenous leukaemia ,BCR-ABL1 ,standardization ,international scale ,therapymonitoring ,Reliability engineering ,030220 oncology & carcinogenesis ,Human medicine ,business ,030215 immunology - Abstract
Introduction: Standardization of BCR-ABL1 messenger RNA quantifi-cation by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results. Methods: To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA)data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results.R esults and conclusion: We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the pro-posed method is a valuable alternative. We thank all the members of the Belgian workinggroup on BCR-ABL1 standardization for sharing theEQA data. We are grateful to Prof. David Barnett andMr Stuart Scott for reviewing the manuscript and forallowing us to use and interpret UKNEQAS LI data aswe feel appropriate. This work was supported byNovartis Pharma.
- Published
- 2016
11. Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia.
- Author
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Maes, J., Devos, H., Cauwelier, B., De Paepe, P., and Emmerechts, J.
- Subjects
- *
NUCLEOTIDE sequencing , *TYPE I interferons , *ACUTE myeloid leukemia , *DENDRITIC cells , *CELL populations , *BLAST injuries - Abstract
This article discusses a case study of a 72-year-old man with essential thrombocythemia who was diagnosed with mature plasmacytoid dendritic cell proliferation (MPDCP) associated with acute myeloid leukemia (AML). The patient presented with symptoms such as dizziness, night sweats, and weight loss. The diagnosis was confirmed through bone marrow examination and flow cytometric analysis. The article also mentions the classification of neoplasms involving plasmacytoid dendritic cells (pDCs) and the need for further research on the immunophenotype and genomic landscape of pDC-AML. [Extracted from the article]
- Published
- 2024
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12. Evaluation of two automated cell counters for the analysis of hematopoietic progenitor cell apheresis products
- Author
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Gils, S., primary, Cauwelier, B., additional, Devos, H., additional, Vanlaere, I., additional, Roggeman, S., additional, and Emmerechts, J., additional
- Published
- 2017
- Full Text
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13. A novel approach for BCR-ABL1 standardization to improve International Scale estimation
- Author
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UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de thérapie tissulaire et cellulaire, UCL - (SLuc) Service de biologie hématologique, Maes, B, Bakkus, M, Boeckx, N, Boone, E, Cauwelier, B, Denys, B, De Schouwer, P, Devos, T, El Housni, H, Hillen, F, Jacobs, K, Lambert, F, Louagie, H, Maes, M-B, Meeus, P, Moreau, E, Nollet, F, Peeters, K, Saussoy, Pascale, Van Lint, P, Vaerman, Jean-Luc, Vaeyens, F, Vandepoele, K, Vannuffel, P, Ver Elst, K, Vermeulen, K, Bruyndonckx, R, Belgian working group on BCR-ABL1 IS standardization, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de thérapie tissulaire et cellulaire, UCL - (SLuc) Service de biologie hématologique, Maes, B, Bakkus, M, Boeckx, N, Boone, E, Cauwelier, B, Denys, B, De Schouwer, P, Devos, T, El Housni, H, Hillen, F, Jacobs, K, Lambert, F, Louagie, H, Maes, M-B, Meeus, P, Moreau, E, Nollet, F, Peeters, K, Saussoy, Pascale, Van Lint, P, Vaerman, Jean-Luc, Vaeyens, F, Vandepoele, K, Vannuffel, P, Ver Elst, K, Vermeulen, K, Bruyndonckx, R, and Belgian working group on BCR-ABL1 IS standardization
- Abstract
INTRODUCTION: Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results. METHODS: To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA) data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results. RESULTS AND CONCLUSION: We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the proposed method is a valuable alternative.
- Published
- 2016
14. Evaluation of the Red Blood Cell Advanced Software Application on the CellaVision DM96
- Author
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Criel, M., primary, Godefroid, M., additional, Deckers, B., additional, Devos, H., additional, Cauwelier, B., additional, and Emmerechts, J., additional
- Published
- 2016
- Full Text
- View/download PDF
15. PHF6 mutations in T-cell lymphoblastic leukemia
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Vlierberghe, P, Palomero, T, Khiabanian, H, van der Meulen, J, Castillo, M, van Roy, N, de Moerloose, B, Philippe, J, Conzalez-Garcia, S, Toribio, ML, Taghon, T, Zuurbier, Linda, Cauwelier, B, Harrison, CJ, Schwab, C, Pisecker, M, Strehl, S, Langerak, Ton, Gecz, J, Sonneveld, E, Pieters, Rob, Paietta, E, Rowe, J, Wiernik, PH, Benoit, Y, Soulier, J, Poppe, B, Yao, X, Cordon-Cardo, C, Meijerink, Jules, Rabadan, R, Speleman, F, Ferrando, AA, Pediatrics, and Immunology
- Published
- 2010
16. Hedgehog pathway mutations in T-cell acute lymphoblastic leukemia
- Author
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Dagklis, A., primary, Pauwels, D., additional, Lahortiga, I., additional, Geerdens, E., additional, Bittoun, E., additional, Cauwelier, B., additional, Tousseyn, T., additional, Uyttebroeck, A., additional, Maertens, J., additional, Verhoef, G., additional, Vandenberghe, P., additional, and Cools, J., additional
- Published
- 2014
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17. A novel HLA-C null allele,HLA-C*05:99N
- Author
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Cauwelier, B., primary, Nollet, F., additional, Gadisseur, A., additional, Schroyens, W., additional, and Berneman, Z., additional
- Published
- 2014
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- View/download PDF
18. PHF6 mutations in T-cell acute lymphoblastic leukemia
- Author
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Vlierberghe, P. (Pieter) van, Palomero, T. (Teresa), Khiabanian, H. (Hossein), Meulen, J. (Joni) van der, Castillo, M. (Mireia), Roy, N. (Nadine) van, Moerloose, B. (Barbara) de, Philippé, J. (Jan), González-García, S. (Sara), Toribio, M.L. (María), Taghon, T. (Tom), Zuurbier, L.C. (Linda), Cauwelier, B. (Barbara), Harrison, C.J. (Christine), Schwab, C. (Claire), Pisecker, M. (Markus), Strehl, S., Langerak, A.W. (Anton), Gecz, J. (Jozef), Sonneveld, E. (Edwin), Pieters, R. (Rob), Paietta, E. (Elisabeth), Rowe, J. (Jacob), Wiernik, P.H. (Peter), Benoit, Y. (Yves), Soulier, J. (Jean), Poppe, B. (Bruce), Yao, X. (Xiaopan), Cordon-Cardo, C. (Carlos), Meijerink, J.P.P. (Jules), Rabadan, R. (Raul), Speleman, F. (Franki), Ferrando, A.A. (Adolfo), Vlierberghe, P. (Pieter) van, Palomero, T. (Teresa), Khiabanian, H. (Hossein), Meulen, J. (Joni) van der, Castillo, M. (Mireia), Roy, N. (Nadine) van, Moerloose, B. (Barbara) de, Philippé, J. (Jan), González-García, S. (Sara), Toribio, M.L. (María), Taghon, T. (Tom), Zuurbier, L.C. (Linda), Cauwelier, B. (Barbara), Harrison, C.J. (Christine), Schwab, C. (Claire), Pisecker, M. (Markus), Strehl, S., Langerak, A.W. (Anton), Gecz, J. (Jozef), Sonneveld, E. (Edwin), Pieters, R. (Rob), Paietta, E. (Elisabeth), Rowe, J. (Jacob), Wiernik, P.H. (Peter), Benoit, Y. (Yves), Soulier, J. (Jean), Poppe, B. (Bruce), Yao, X. (Xiaopan), Cordon-Cardo, C. (Carlos), Meijerink, J.P.P. (Jules), Rabadan, R. (Raul), Speleman, F. (Franki), and Ferrando, A.A. (Adolfo)
- Abstract
Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.
- Published
- 2010
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19. Modulation of Mir-449a Expression Decreases Cell Viability, Increases Apoptosis and Induces Differentiation in Evi1 Deregulated Leukemia Cells
- Author
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UCL - Cliniques universitaires Saint-Luc, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, De Weer, A., Poirel, Hélène, Poppe, B., Mestdagh, P., De Preter, K., Van Vlierberghe, P., Van Roy, N., Jeison, M., Cauwelier, B., Verhasselt, B., Philippé, Jan, Noens, L., Vandenberghe, Peter, Lambert, F., De Paepe, A., Dastugue, N., Vandesompele, J., Speleman, F., 14th Annual Meeting of the European-Hematology-Association, UCL - Cliniques universitaires Saint-Luc, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, De Weer, A., Poirel, Hélène, Poppe, B., Mestdagh, P., De Preter, K., Van Vlierberghe, P., Van Roy, N., Jeison, M., Cauwelier, B., Verhasselt, B., Philippé, Jan, Noens, L., Vandenberghe, Peter, Lambert, F., De Paepe, A., Dastugue, N., Vandesompele, J., Speleman, F., and 14th Annual Meeting of the European-Hematology-Association
- Published
- 2009
20. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCR beta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique
- Author
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UCL - MD/MINT - Département de médecine interne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Cauwelier, B., Lefebvre, Christine, Leroux, Dominique, Poirel, Héléne, Graux, Carlos, Cools, Jan, Hagemeijer, Anne, UCL - MD/MINT - Département de médecine interne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Cauwelier, B., Lefebvre, Christine, Leroux, Dominique, Poirel, Héléne, Graux, Carlos, Cools, Jan, and Hagemeijer, Anne
- Abstract
Recently, we and others described a new chromosomal rearrangement, that is, inv( 7)( p15q34) and t( 7; 7)( p15; q34) involving the T-cell receptor beta ( TCR beta) ( 7q34) and the HOXA gene locus ( 7p15) in 5% of T-cell acute lymphoblastic leukemia ( T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCR beta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients ( 3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCR beta-HOXA rearrangement ( 8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCR beta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCR beta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL ( SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRb- HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCR beta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
- Published
- 2007
21. The TCRB-HOXA rearrangement in T-ALL leads to a specific increase of the alternative HOXA10b transcript
- Author
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UCL, Cauwelier, B., Cave, H., Dastugue, N., Heimann, P., Antoine-Poirel, Helene, Verhasselt, B., Benoit, Y., De Moerloose, B., Van Roy, N., Hagemeijer, Anne, De Paepe, A., Speleman, F., UCL, Cauwelier, B., Cave, H., Dastugue, N., Heimann, P., Antoine-Poirel, Helene, Verhasselt, B., Benoit, Y., De Moerloose, B., Van Roy, N., Hagemeijer, Anne, De Paepe, A., and Speleman, F.
- Published
- 2006
22. HOXA11 (homeobox A11)
- Author
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Cauwelier, B, primary and Speleman, F, additional
- Published
- 2011
- Full Text
- View/download PDF
23. inv(7)(p15q34) - t(7;7)(p15;q34)
- Author
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Cauwelier, B, primary, Dastugue, N, additional, Hagemeijer, A, additional, and Speleman, F, additional
- Published
- 2011
- Full Text
- View/download PDF
24. Screening for EVI1: ectopic expression absent in T-cell acute lymphoblastic leukemia patients and cell lines
- Author
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De Weer, A., primary, Poppe, B., additional, Cauwelier, B., additional, Van Roy, N., additional, Dastugue, N., additional, Hagemeijer, A., additional, De Paepe, A., additional, and Speleman, F., additional
- Published
- 2006
- Full Text
- View/download PDF
25. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique
- Author
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Cauwelier, B, primary, Cavé, H, additional, Gervais, C, additional, Lessard, M, additional, Barin, C, additional, Perot, C, additional, Van den Akker, J, additional, Mugneret, F, additional, Charrin, C, additional, Pagès, M P, additional, Grégoire, M-J, additional, Jonveaux, P, additional, Lafage-Pochitaloff, M, additional, Mozzicconacci, M J, additional, Terré, C, additional, Luquet, I, additional, Cornillet-Lefebvre, P, additional, Laurence, B, additional, Plessis, G, additional, Lefebvre, C, additional, Leroux, D, additional, Antoine-Poirel, H, additional, Graux, C, additional, Mauvieux, L, additional, Heimann, P, additional, Chalas, C, additional, Clappier, E, additional, Verhasselt, B, additional, Benoit, Y, additional, Moerloose, B D, additional, Poppe, B, additional, Van Roy, N, additional, Keersmaecker, K D, additional, Cools, J, additional, Sigaux, F, additional, Soulier, J, additional, Hagemeijer, A, additional, Paepe, A D, additional, Dastugue, N, additional, Berger, R, additional, and Speleman, F, additional
- Published
- 2006
- Full Text
- View/download PDF
26. P66: Identification of genes involved in T-cell oncogenesis through FISH screening of TCR rearrangements in T-ALL
- Author
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Van Roy, N, primary, Cauwelier, B, additional, Speleman, F, additional, Dastugue, N, additional, Cools, J, additional, Verhasselt, B, additional, Poppe, B, additional, Vandesompele, J, additional, Boogaerts, M, additional, De Moerloose, B, additional, Benoit, Y, additional, Selleslag, D, additional, Billiet, J, additional, Huguet, F, additional, Vandenberghe, P, additional, De Paepe, A, additional, Marynen, P, additional, and Hagemeijer, A, additional
- Published
- 2005
- Full Text
- View/download PDF
27. Evaluation of a disk diffusion method with cefoxitin (30��g) for detection of methicillin-resistant Staphylococcus aureus
- Author
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Van Landuyt, H., primary, Cauwelier, B., additional, Gordts, B., additional, and Descheemaecker, P., additional
- Published
- 2004
- Full Text
- View/download PDF
28. Simultaneous Occurrence of Myelodysplastic Syndrome and Monoclonal B Lymphocytes with a Different Clonal Origin
- Author
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Cauwelier, B., primary, Nollet, F., additional, Laere, E. De, additional, Leeuwen, M. Van, additional, Billiet, J., additional, Criel, A., additional, and Louwagie, A., additional
- Published
- 2002
- Full Text
- View/download PDF
29. Hematological and pathological effects of 0.25% purified simmondsin in growing rats
- Author
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Cokelaere, M, primary, Cauwelier, B, additional, Cokelaere, K, additional, Flo, G, additional, Houache, N, additional, Lievens, S, additional, Van Boven, M, additional, and Decuypere, E, additional
- Published
- 2000
- Full Text
- View/download PDF
30. A novel HLA-C null allele, HLA-C*05: 99N.
- Author
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Cauwelier, B., Nollet, F., Gadisseur, A., Schroyens, W., and Berneman, Z.
- Subjects
- *
ALLELES , *HLA histocompatibility antigens , *NUCLEOTIDE sequence , *SINGLE nucleotide polymorphisms , *HUMAN genetics , *LEUCOCYTES - Abstract
HLA-C*05:99N results from a single nucleotide loss compared with its closest allele HLA-C*05:01:01:01. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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31. EVI1 activation in blast crisis CML due to juxtaposition to the rare 17q22 partner region as part of a 4-way variant translocation t(9;22).
- Author
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De Weer A, Poppe B, Cauwelier B, Carlier A, Dierick J, Verhasselt B, Philippé J, Van Roy N, Speleman F, De Weer, An, Poppe, Bruce, Cauwelier, Barbara, Carlier, Andre, Dierick, Jan, Verhasselt, Bruno, Philippé, Jan, Van Roy, Nadine, and Speleman, Frank
- Abstract
Background: Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed CMLs and additional genetic changes are present in 60-80% of patients in blast crisis (BC). Here, we report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the EVI1 locus.Methods: Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of EVI1 and BCR/ABL1 were investigated using real-time quantitative RT-PCR.Results: In this paper we identified a patient with a complex 4-way t(3;9;17;22) which, in addition to BCR/ABL1 gene fusion, also resulted in EVI1 rearrangement and overexpression.Conclusion: This report illustrates how a variant t(9;22) translocation can specifically target a second oncogene most likely contributing to the more aggressive phenotype of the disease. Molecular analysis of such variants is thus warranted to understand the phenotypic consequences and to open the way for combined molecular therapies in order to tackle the secondary oncogenic effect which is unresponsive to imatinib treatment. [ABSTRACT FROM AUTHOR]- Published
- 2008
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32. Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high-grade B-cell lymphoma (HGBL) and diffuse large B-cell lymphoma (DLBCL): Can we identify different prognostic subgroups?
- Author
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Blomme S, De Paepe P, Devos H, Emmerechts J, Snauwaert S, and Cauwelier B
- Subjects
- Humans, Gene Rearrangement, In Situ Hybridization, Fluorescence, Prognosis, Proto-Oncogene Proteins c-bcl-6 genetics, Proto-Oncogene Proteins c-myc genetics, Retrospective Studies, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Proto-Oncogene Proteins c-bcl-2 genetics
- Abstract
High-grade B-cell lymphoma (HGBL)/diffuse large B-cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC-R and BCL2-R and/or BCL6-R-samples with MYC-R and BCL2-R (+/- BCL6-R); n = 21, and HGBL/DLBCL with MYC-R and BCL6-R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called "alternative HGBL/DLBCL"-samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) "No alterations" (n = 55). Patients with HGBL/DLBCL-MYC/BCL2 and "alternative" HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the "no alterations" group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC-R and BCL6-R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL-MYC/BCL2. According to immunohistochemistry, "double/triple" expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups., (© 2023 Wiley Periodicals LLC.)
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- 2024
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33. Parvovirus B19-triggered hemophagocytic lymphohistiocytosis in a patient with Crohn's disease.
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Debels L, Reynders M, Cauwelier B, Willandt B, Selleslag D, and Snauwaert C
- Subjects
- Adult, Child, Cytokines, Ferritins, Humans, Interleukin-12, Male, Ustekinumab therapeutic use, Crohn Disease complications, Crohn Disease drug therapy, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic drug therapy, Lymphohistiocytosis, Hemophagocytic etiology, Parvoviridae Infections complications, Parvoviridae Infections diagnosis, Parvovirus B19, Human
- Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition caused by inappropriate immune activity. Infection is often the trigger, both in genetically predisposed and in sporadic cases. Although more commonly seen in the paediatric population, patients of all ages can be affected., Case Presentation: A 26-year-old male patient with Crohn's disease, treated with ustekinumab, presented with high fever, epistaxis and anorexia. Laboratory results showed pancytopenia, and a high serum levels of ferritin and LDH. Colonoscopy revealed only mild signs of disease activity. CT-scan showed splenomegaly and multiple lymphadenopathies. Bone marrow aspirate was suggestive for hemophagocytosis. PCR & serology for parvovirus B19 came back positive. Treatment with ustekinumab was temporarily put on hold and supportive care was given. Viral replication decreased and he recovered completely., Conclusion: There is a known association between HLH and Crohn's disease. This is probably because they are more susceptible to infections with CMV, EBV and parvovirus B19, all known as triggers for HLH. The role of ustekinumab is unclear: did it play a role in the pathophysiological evolution of this primo-infection with parvovirus B19? On the other hand, did it contribute to the rather mild course of the disease, acting as a immunomodulator that works on interleukin-12, a cytokine that plays a role in HLH? Further study is warranted to answer these questions., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)
- Published
- 2022
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34. Routine noninvasive prenatal screening for fetal Rh D in maternal plasma-A 2-year experience from a single center in Belgium.
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Blomme S, Nollet F, Rosseel W, Bogaard N, Devos H, Emmerechts J, and Cauwelier B
- Subjects
- Belgium, Female, Fetus, Genotype, Humans, Pregnancy, Prenatal Diagnosis methods, Rh-Hr Blood-Group System genetics, Rho(D) Immune Globulin, Erythroblastosis, Fetal diagnosis, Erythroblastosis, Fetal prevention & control, Noninvasive Prenatal Testing
- Abstract
Background: Hemolytic disease of the fetus and newborn (HDFN) due to rhesus D (RhD) immunization is a potentially life-threatening situation for which use of Rh Immunoglobulin (RhIg) has decreased risk drastically. Determination of fetal RHD on maternal plasma can be used to restrict prenatal RhIg administration to women carrying an RhD-positive child, avoiding unnecessary administration of blood-derived products., Study Design and Methods: The aim of this study is to determine the performance of fetal RHD typing in our center. We prospectively collected 205 fetal RHD and 127 serological cord blood RhD data from RhD-negative women starting at 11 weeks of pregnancy (from October 2019 to October 2021). Real-time polymerase chain reaction targeting RHD exon 5 and 7 was used, similar to the screening program in The Netherlands, supplemented with an amplification control (beta-actin; ACTB) and a sex determination marker located on the Y-chromosome (SRY gene)., Results: Fetal RHD testing reached a sensitivity and specificity of 100%. No false-negative nor false-positive results were reported. Inconclusive results (6%, 13/205) were due to weak amplification in 10 cases, a maternal RHD variant in 2 cases (RHD*01N.71 and partial DVI), and a fetal RHD variant (partial DVI) in 1 case. Unnecessary administration of RhIg prophylaxis was avoided in 33% of cases and on the other hand was administered in one case (fetal partial DVI) which would have been missed with cord blood serology., Discussion: This study demonstrates the high accuracy of routine prenatal fetal RHD gene screening after 11 weeks of pregnancy, encouraging routine clinical practice., (© 2022 AABB.)
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- 2022
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35. Performance Assessment of the Devyser High-Throughput Sequencing-Based Assay for Chimerism Monitoring in Patients after Allogeneic Hematopoietic Stem Cell Transplantation.
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Vynck M, Nollet F, Sibbens L, Lievens B, Denys A, Cauwelier B, and Devos H
- Subjects
- Electrophoresis, Capillary methods, Humans, Laboratories, Clinical, Limit of Detection, Microsatellite Repeats genetics, Monitoring, Physiologic methods, Polymerase Chain Reaction methods, Reproducibility of Results, Transplantation, Homologous, Chimerism, Hematopoietic Stem Cell Transplantation, High-Throughput Nucleotide Sequencing methods
- Abstract
Chimerism analysis is widely used to aid in the clinical management of patients after allogeneic hematopoietic stem cell transplantation. Many laboratories currently use assays based on PCR followed by capillary electrophoresis, with a limit of quantification of 1% to 5%. Assays with a lower limit of quantification could allow for earlier relapse detection, resulting in improved patient care. This study investigated the analytical, clinical, technical, and practical performance of the Devyser next-generation sequencing chimerism assay, a commercial high-throughput sequencing-based assay for chimerism analysis. Performance of this assay was compared with that of the Promega PowerPlex 16 HS assay, a commercial capillary electrophoresis-based assay. A limit of quantification of 0.1% was achievable with the Devyser assay. The repeatability, reproducibility, trueness, and linearity of the Devyser assay were acceptable. The Devyser assay showed potential for earlier relapse detection compared with the Promega assay. Conclusive analysis was not possible for 3% of donor-recipient pairs with the Devyser assay due to an insufficient number of informative markers; this factor was not an issue for the Promega assay. Further improvements in assay design or data analysis may allow the assay's applicability to be extended to all donor-recipient pairs studied. Technical performance criteria for chimerism analysis by high-throughput sequencing were suggested and evaluated. Both assays were found to be practical for use in a clinical diagnostics laboratory., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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36. Diagnostic utility of the lymphoid screening tube supplemented with CD34 for Ogata score calculation in patients with peripheral cytopenia.
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Muyldermans A, Florin L, Devos H, Cauwelier B, and Emmerechts J
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- Adolescent, Adult, Aged, Aged, 80 and over, Bone Marrow pathology, Female, Humans, Leukocyte Common Antigens blood, Male, Middle Aged, Myelodysplastic Syndromes pathology, Plasma Cells metabolism, Plasma Cells pathology, Antigens, CD34 blood, Bone Marrow metabolism, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes diagnosis
- Abstract
Objectives: The diagnosis of myelodysplastic syndrome (MDS) is not always straightforward in the absence of objective markers such as ringed sideroblasts, an excess of blasts or clonal cytogenetic abnormalities. Moreover, the lack of specificity of morphological dysplasia makes the differentiation between MDS and other causes of peripheral cytopenia difficult. The WHO 2016 classification of MDS recognizes multiparameter flow cytometry (MFC) as an adjuvant tool for MDS diagnosis. An easily applicable MFC protocol based on CD34 and CD45 is proposed by Ogata et al. Furthermore, in the diagnostic workup of patients with peripheral cytopenia, the integration of MFC by means of a Lymphoid Screening Tube (LST) is recommended by the EuroFlow™ consortium. The aim of this study was to investigate whether the LST, supplemented with CD34, can be used to calculate the Ogata score, thereby obviating the need to run different flow cytometric tubes., Methods: Bone marrow samples from 108 patients with peripheral cytopenia were analyzed (MDS n = 32; non-MDS n = 76). The LST used in the present study was based on the tube designed by the EuroFlow™ consortium, but with addition of CD34 and without TCRγδ., Results: Rather low sensitivities of 55% in low-grade MDS patients and 80% in high-grade MDS patients were observed. However, a high specificity of 92% was found in the non-MDS group., Conclusion: Besides screening for clonal lymphocytes, plasma cells and blasts, an LST supplemented with CD34 allows the calculation of the Ogata score as an adjuvant tool in the diagnostic workup of cytopenic patients suspected of MDS.
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- 2019
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37. Evaluation of next-generation sequencing-based clonality analysis of T-cell receptor gamma gene rearrangements based on a new interpretation algorithm.
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Nollet F, Vanhouteghem K, Vermeire S, Maelbrancke E, Emmerechts J, Devos H, and Cauwelier B
- Subjects
- Female, Humans, Male, Algorithms, Gene Rearrangement, Hematologic Neoplasms genetics, High-Throughput Nucleotide Sequencing, Receptors, Antigen, T-Cell, gamma-delta genetics, Sequence Analysis, DNA
- Abstract
Introduction: T-cell receptor gene (TRG) rearrangement profiling is an essential component of the workup at diagnosis of T-cell malignancies. TRG amplification by polymerase chain reaction (PCR) and analysis by capillary electrophoresis (PCR-CE) is mostly widely used but is hampered by a subjective interpretation of its results and possible false-positive interpretation of clonality. Several studies evaluated the advantage of TRG rearrangement analysis by Next Generation Sequencing (TRG-NGS), however few have proposed an adequate data interpretation algorithm., Methods: Eighty five fresh and 36 formalin-fixed paraffin embedded (FFPE) diagnostic samples suspected for a lymphoproliferative disorder were analyzed by PCR-CE and TRG NGS. Final clinical diagnosis was available for all fresh samples. Reproducibility, analytical specificity and sensitivity of the TRG NGS analysis was evaluated., Results: We propose a new interpretation algorithm for TRG NGS data analysis. PCR-CE and TRG NGS showed identical results in 66/85 (78%) of fresh samples. Sensitivities to detect T-cell malignancies were comparable (96% versus 92%, respectively). The analysis of FFPE material was significantly more successful by TRG NGS (34/36 cases) in respect to PCR-CE (16/36 cases), most likely due to the small size of the amplicons., Conclusion: Assessment of T-cell clonality by TRG NGS has a significant added value in the diagnosis of T-cell disorders as an adjunct to PCR-CE, particularly in difficult to interpret cases or when analyzing FFPE samples., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2019
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38. Evaluation of four hemoglobin separation analyzers for hemoglobinopathy diagnosis.
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Degandt S, Coens R, Cauwelier B, Devos H, Langlois M, and Emmerechts J
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- Aged, Female, Humans, Reproducibility of Results, Sensitivity and Specificity, Chromatography, High Pressure Liquid methods, Electrophoresis, Capillary methods, Hematologic Tests methods, Hemoglobinopathies diagnosis, Hemoglobins analysis, Hemoglobins isolation & purification
- Abstract
Background: Four automated hemoglobin separation devices are compared in their ability to detect hemoglobinopathies, both in HbA1c and in hemoglobinopathy mode., Methods: Quality control material and 58 samples, including one heterozygous α-thalassemia sample, six heterozygote β-thalassemia samples and 32 samples with a known hemoglobin variant, were used to assess imprecision of HbF and HbA2 measurements, correlation with the gold standard and sensitivity for detecting β-thalassemia and Hb variants on D-100 (Bio-Rad Laboratories), HA 8180T (Menarini), HLC-723G8 (Tosoh Bioscience) and Capillarys 2 Flex Piercing (Sebia)., Results: Imprecision was <10% for both HbF and HbA2 in all modes of all analyzers. Correlation studies for HbF and HbA2 demonstrated statistically significant but small biases when compared to the gold standard. All six β-thalassemia samples but one were detected on all analyzers using a HbA2 cut-off value of 3.5%. D-100, HA8180T and the Hb-pathy mode of the HLC-723G8 and the Capillarys are able to detect the most common important Hb variants (Hb C, D, E and S), but more seldom variants can be missed as they co-elute with HbA0. The HbA1c mode of the Capillarys correctly detected all measured hemoglobin variants and can therefore be used as a hemoglobinopathy screening device. This was also the case for the most common important Hb variants on the HbA1c mode of the HLC-723G8, but two rare variants were not detected., Conclusion: This study stresses the importance for individual laboratories to know the advantages and drawbacks of their hemoglobin separation analyzer and its different modes in the diagnosis of hemoglobinopathies., (© 2017 Wiley Periodicals, Inc.)
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- 2018
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39. A novel approach for BCR-ABL1 standardization to improve International Scale estimation.
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Maes B, Bakkus M, Boeckx N, Boone E, Cauwelier B, Denys B, De Schouwer P, Devos T, El Housni H, Hillen F, Jacobs K, Lambert F, Louagie H, Maes MB, Meeus P, Moreau E, Nollet F, Peeters K, Saussoy P, Van Lint P, Vaerman JL, Vaeyens F, Vandepoele K, Vannuffel P, Ver Elst K, Vermeulen K, and Bruyndonckx R
- Subjects
- Genetic Testing, International Cooperation, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Methods, Observer Variation, Reference Standards, Retrospective Studies, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, RNA, Messenger analysis
- Abstract
Introduction: Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results., Methods: To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA) data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results., Results and Conclusion: We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the proposed method is a valuable alternative., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
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40. Hedgehog pathway mutations in T-cell acute lymphoblastic leukemia.
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Dagklis A, Pauwels D, Lahortiga I, Geerdens E, Bittoun E, Cauwelier B, Tousseyn T, Uyttebroeck A, Maertens J, Verhoef G, Vandenberghe P, and Cools J
- Subjects
- Adolescent, Adult, Animals, Base Sequence, Child, Female, Gene Expression, HEK293 Cells, Humans, Kruppel-Like Transcription Factors immunology, Male, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Nerve Tissue Proteins immunology, Patched Receptors, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology, Receptors, Cell Surface immunology, Receptors, G-Protein-Coupled immunology, Signal Transduction, Smoothened Receptor, T-Lymphocytes immunology, T-Lymphocytes pathology, T-Lymphocytes transplantation, Transcription Factors immunology, Transduction, Genetic, Zinc Finger Protein GLI1, Zinc Finger Protein Gli3, Kruppel-Like Transcription Factors genetics, Nerve Tissue Proteins genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Receptors, Cell Surface genetics, Receptors, G-Protein-Coupled genetics, Transcription Factors genetics
- Published
- 2015
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41. Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia.
- Author
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De Keersmaecker K, Atak ZK, Li N, Vicente C, Patchett S, Girardi T, Gianfelici V, Geerdens E, Clappier E, Porcu M, Lahortiga I, Lucà R, Yan J, Hulselmans G, Vranckx H, Vandepoel R, Sweron B, Jacobs K, Mentens N, Wlodarska I, Cauwelier B, Cloos J, Soulier J, Uyttebroeck A, Bagni C, Hassan BA, Vandenberghe P, Johnson AW, Aerts S, and Cools J
- Subjects
- Animals, Base Sequence, Drosophila melanogaster, High-Throughput Nucleotide Sequencing, Humans, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutation genetics, Polyribosomes genetics, RNA Interference, Ribosomal Protein L10, Saccharomyces cerevisiae, Sequence Alignment, Exome genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics, Ribosomal Proteins genetics, Transcription Factors genetics
- Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is caused by the cooperation of multiple oncogenic lesions. We used exome sequencing on 67 T-ALLs to gain insight into the mutational spectrum in these leukemias. We detected protein-altering mutations in 508 genes, with an average of 8.2 mutations in pediatric and 21.0 mutations in adult T-ALL. Using stringent filtering, we predict seven new oncogenic driver genes in T-ALL. We identify CNOT3 as a tumor suppressor mutated in 7 of 89 (7.9%) adult T-ALLs, and its knockdown causes tumors in a sensitized Drosophila melanogaster model. In addition, we identify mutations affecting the ribosomal proteins RPL5 and RPL10 in 12 of 122 (9.8%) pediatric T-ALLs, with recurrent alterations of Arg98 in RPL10. Yeast and lymphoid cells expressing the RPL10 Arg98Ser mutant showed a ribosome biogenesis defect. Our data provide insights into the mutational landscape of pediatric versus adult T-ALL and identify the ribosome as a potential oncogenic factor.
- Published
- 2013
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42. Mutation of the receptor tyrosine phosphatase PTPRC (CD45) in T-cell acute lymphoblastic leukemia.
- Author
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Porcu M, Kleppe M, Gianfelici V, Geerdens E, De Keersmaecker K, Tartaglia M, Foà R, Soulier J, Cauwelier B, Uyttebroeck A, Macintyre E, Vandenberghe P, Asnafi V, and Cools J
- Subjects
- Amino Acid Sequence, Cell Line, Tumor, Cell Proliferation drug effects, Gene Expression Regulation, Leukemic drug effects, Genes, Tumor Suppressor drug effects, Genes, Tumor Suppressor physiology, HEK293 Cells, Humans, Janus Kinases metabolism, Leukocyte Common Antigens antagonists & inhibitors, Leukocyte Common Antigens metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology, RNA, Small Interfering pharmacology, STAT Transcription Factors metabolism, Signal Transduction drug effects, Signal Transduction genetics, Leukocyte Common Antigens genetics, Mutation physiology, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
The protein tyrosine phosphatase CD45, encoded by the PTPRC gene, is well known as a regulator of B- and T-cell receptor signaling. In addition, CD45 negatively regulates JAK family kinases downstream of cytokine receptors. Here, we report the presence of CD45 inactivating mutations in T-cell acute lymphoblastic leukemia. Loss-of-function mutations of CD45 were detected in combination with activating mutations in IL-7R, JAK1, or LCK, and down-regulation of CD45 expression caused increased signaling downstream of these oncoproteins. Furthermore, we demonstrate that down-regulation of CD45 expression sensitizes T cells to cytokine stimulation, as observed by increased JAK/STAT signaling, whereas overexpression of CD45 decreases cytokine-induced signaling. Taken together, our data identify a tumor suppressor role for CD45 in T-cell acute lymphoblastic leukemia.
- Published
- 2012
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43. EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells.
- Author
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De Weer A, Van der Meulen J, Rondou P, Taghon T, Konrad TA, De Preter K, Mestdagh P, Van Maerken T, Van Roy N, Jeison M, Yaniv I, Cauwelier B, Noens L, Poirel HA, Vandenberghe P, Lambert F, De Paepe A, Sánchez MG, Odero M, Verhasselt B, Philippé J, Vandesompele J, Wieser R, Dastugue N, Van Vlierberghe P, Poppe B, and Speleman F
- Subjects
- Adult, Aged, Aged, 80 and over, Apoptosis genetics, Cell Survival, DNA-Binding Proteins metabolism, Gene Expression Profiling methods, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Infant, Leukemia genetics, Leukemia pathology, MDS1 and EVI1 Complex Locus Protein, MicroRNAs genetics, Middle Aged, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Proto-Oncogene Proteins c-bcl-2 physiology, RNA, Neoplasm genetics, Receptor, Notch1 biosynthesis, Receptor, Notch1 physiology, Regulatory Elements, Transcriptional physiology, Transcription Factors metabolism, Tumor Cells, Cultured, DNA-Binding Proteins physiology, Down-Regulation physiology, Leukemia metabolism, MicroRNAs biosynthesis, Proto-Oncogenes physiology, Transcription Factors physiology
- Abstract
Chromosomal rearrangements involving the MECOM (MDS1 and EVI1 complex) locus are recurrent genetic events in myeloid leukaemia and are associated with poor prognosis. In this study, we assessed the role of MECOM locus protein EVI1 in the transcriptional regulation of microRNAs (miRNAs) involved in the leukaemic phenotype. For this, we profiled expression of 366 miRNAs in 38 MECOM-rearranged patient samples, normal bone marrow controls and MECOM (EVI1) knock down/re-expression models. Cross-comparison of these miRNA expression profiling data showed that MECOM rearranged leukaemias are characterized by down regulation of MIR449A. Reconstitution of MIR449A expression in MECOM-rearranged cell line models induced apoptosis resulting in a strong decrease in cell viability. These effects might be mediated in part by MIR449A regulation of NOTCH1 and BCL2, which are shown here to be bona fide MIR449A targets. Finally, we confirmed that MIR449A repression is mediated through direct promoter occupation of the EVI1 transcriptional repressor. In conclusion, this study reveals MIR449A as a crucial direct target of the MECOM locus protein EVI1 involved in the pathogenesis of MECOM-rearranged leukaemias and unravels NOTCH1 and BCL2 as important novel targets of MIR449A. This EVI1-MIR449A-NOTCH1/BCL2 regulatory axis might open new possibilities for the development of therapeutic strategies in this poor prognostic leukaemia subgroup., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2011
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44. JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma.
- Author
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Van Roosbroeck K, Cox L, Tousseyn T, Lahortiga I, Gielen O, Cauwelier B, De Paepe P, Verhoef G, Marynen P, Vandenberghe P, De Wolf-Peeters C, Cools J, and Wlodarska I
- Subjects
- Adult, Aged, 80 and over, Animals, Bone Marrow Transplantation, Chromosomes, Human, Pair 4, Chromosomes, Human, Pair 9, Disease Models, Animal, Female, Genetic Predisposition to Disease epidemiology, HEK293 Cells, Hodgkin Disease epidemiology, Humans, Male, Mice, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Prevalence, Protein-Tyrosine Kinases metabolism, Translocation, Genetic, Young Adult, Gene Rearrangement genetics, Hodgkin Disease genetics, Janus Kinase 2 genetics, Oncogene Proteins, Fusion genetics, Vesicular Transport Proteins genetics
- Abstract
The genetics of classical Hodgkin lymphoma (cHL) is poorly understood. The finding of a JAK2-involving t(4;9)(q21;p24) in 1 case of cHL prompted us to characterize this translocation on a molecular level and to determine the prevalence of JAK2 rearrangements in cHL. We showed that the t(4;9)(q21;p24) leads to a novel SEC31A-JAK2 fusion. Screening of 131 cHL cases identified 1 additional case with SEC31A-JAK2 and 2 additional cases with rearrangements involving JAK2. We demonstrated that SEC31A-JAK2 is oncogenic in vitro and acts as a constitutively activated tyrosine kinase that is sensitive to JAK inhibitors. In vivo, SEC31A-JAK2 was found to induce a T-lymphoblastic lymphoma or myeloid phenotype in a murine bone marrow transplantation model. Altogether, we identified SEC31A-JAK2 as a chromosomal aberration characteristic for cHL and provide evidence that JAK2 rearrangements occur in a minority of cHL cases. Given the proven oncogenic potential of this novel fusion, our studies provide new insights into the pathogenesis of cHL and indicate that in at least some cases, constitutive activation of the JAK/STAT pathway is caused by JAK2 rearrangements. The finding that SEC31A-JAK2 responds to JAK inhibitors indicates that patients with cHL and JAK2 rearrangements may benefit from targeted therapies.
- Published
- 2011
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45. PHF6 mutations in T-cell acute lymphoblastic leukemia.
- Author
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Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N, De Moerloose B, Philippé J, González-García S, Toribio ML, Taghon T, Zuurbier L, Cauwelier B, Harrison CJ, Schwab C, Pisecker M, Strehl S, Langerak AW, Gecz J, Sonneveld E, Pieters R, Paietta E, Rowe JM, Wiernik PH, Benoit Y, Soulier J, Poppe B, Yao X, Cordon-Cardo C, Meijerink J, Rabadan R, Speleman F, and Ferrando A
- Subjects
- Adult, Child, Comparative Genomic Hybridization, DNA Copy Number Variations, Female, Genetic Linkage, Humans, Male, Mutation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Repressor Proteins, Carrier Proteins genetics, Chromosomes, Human, X, Genes, Tumor Suppressor, Homeodomain Proteins genetics, Proto-Oncogene Proteins genetics
- Abstract
Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.
- Published
- 2010
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46. EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22.
- Author
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De Weer A, Speleman F, Cauwelier B, Van Roy N, Yigit N, Verhasselt B, De Moerloose B, Benoit Y, Noens L, Selleslag D, Lippert E, Struski S, Bastard C, De Paepe A, Vandenberghe P, Hagemeijer A, Dastugue N, and Poppe B
- Subjects
- Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 3, DNA-Binding Proteins analysis, Humans, MDS1 and EVI1 Complex Locus Protein, Oncogene Proteins, Fusion genetics, Transcription Factors analysis, DNA-Binding Proteins genetics, Myeloproliferative Disorders genetics, Proto-Oncogenes genetics, RNA-Binding Proteins genetics, Transcription Factors genetics, Translocation, Genetic
- Abstract
Chromosomal translocations involving the EVI1 locus are a recurrent finding in myeloid leukemia and are associated with poor prognosis. In this study, we performed a detailed molecular characterization of the recurrent translocation t(3;17)(q26;q22) in 13 hematologic malignancies. The EVI1 gene locus was rearranged in all 13 patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 (musashi homologue 2) gene. Expression analyses failed to demonstrate ectopic MSI2 expression or the presence of an MSI2/EVI1 fusion gene. In conclusion, we show for the first time that the t(3;17) is indeed a recurrent chromosomal aberration in myeloid malignancies. In keeping with findings in other recurrent 3q26 rearrangements, overexpression of the EVI1 gene appears to be the major contributor to leukemogenesis in patients with a t(3;17).
- Published
- 2008
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47. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.
- Author
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Lahortiga I, De Keersmaecker K, Van Vlierberghe P, Graux C, Cauwelier B, Lambert F, Mentens N, Beverloo HB, Pieters R, Speleman F, Odero MD, Bauters M, Froyen G, Marynen P, Vandenberghe P, Wlodarska I, Meijerink JP, and Cools J
- Subjects
- Cell Differentiation immunology, Cell Line, Tumor, Chromosomes, Artificial genetics, Flow Cytometry, Gene Dosage, Gene Expression Regulation, Neoplastic genetics, Genetic Testing, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Mutation genetics, Nucleic Acid Hybridization genetics, RNA, Small Interfering genetics, Statistics, Nonparametric, Cell Differentiation genetics, Gene Duplication, Genes, myb genetics, Leukemia-Lymphoma, Adult T-Cell genetics, T-Lymphocytes pathology
- Abstract
We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.
- Published
- 2007
- Full Text
- View/download PDF
48. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements.
- Author
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Poppe B, Dastugue N, Vandesompele J, Cauwelier B, De Smet B, Yigit N, De Paepe A, Cervera J, Recher C, De Mas V, Hagemeijer A, and Speleman F
- Subjects
- Adolescent, Adult, Aged, Child, Preschool, Chromosome Inversion, Female, Gene Expression Profiling, Humans, MDS1 and EVI1 Complex Locus Protein, Male, Middle Aged, Physical Chromosome Mapping, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Chromosome Aberrations, Chromosomes, Human, Pair 3, DNA-Binding Proteins genetics, Hematologic Neoplasms genetics, Proto-Oncogenes genetics, Transcription Factors genetics
- Abstract
In contrast to the well-documented involvement of EVI1 in various 3q26 aberrations, the transcriptional status of EVI1 in rare recurrent or sporadic 3q26 chromosomal defects has remained largely unexplored. Moreover, in a recent report, the association between 3q26 alterations in myeloid proliferations and ectopic EVI1 expression was questioned. Therefore, we performed a detailed physical mapping of 3q26 breakpoints using a 1.3-Mb tiling path BAC contig covering the EVI1 locus and a carefully designed quantification of both EVI1 and MDS/EVI1 transcripts in 30 hematological malignancies displaying 3q26 aberrations. Cases included well-known rare, recurring chromosomal aberrations such as t(3;17)(q26;q22), t(2;3)(p21-22;q26), and t(3;6)(q26;q25), as well as 10 new sporadic cases. Extensive 3q26 breakpoint mapping allowed unequivocal and sensitive FISH detection of EVI1 rearrangements on both metaphases and interphase nuclei. Real-time quantitative PCR analyses indicated that typically both MDS1/EVI1 and EVI1, but not MDS1, were expressed in these malignancies, with EVI1 the primary transcript. In conclusion, we have demonstrated EVI1 involvement in numerous novel sporadic and recurrent 3q26 rearrangements. Our results underscore the feasibility of FISH as an adjunct to PCR for the identification of EVI1 deranged leukemias and identified EVI1 as the principal transcript expressed in these malignancies.
- Published
- 2006
- Full Text
- View/download PDF
49. Novel cryptic chromosomal rearrangements in childhood acute lymphoblastic leukemia detected by multiple color fluorescent in situ hybridization.
- Author
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Poppe B, Cauwelier B, Van Limbergen H, Yigit N, Philippé J, Verhasselt B, De Paepe A, Benoit Y, and Speleman F
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Karyotyping methods, Male, In Situ Hybridization, Fluorescence methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Translocation, Genetic genetics
- Abstract
Background and Objectives: It is often difficult to obtain good karyotypes of cells from children with acute lymphoblastic leukemia (ALL) because of poor morphology and spreading. Detailed karyotyping can be further hampered by the presence of multiple rearrangements. Our objective was to search for cryptic rearrangements in childhood ALL., Design and Methods: A series of eight cases of childhood ALL with at least two structural defects were selected and studied by multiple color fluorescent in situ hybridization (M-FISH)., Results: Four previously not reported translocations were detected: a t(14;20) (q32;q11.2) in a 3-year old girl with T-ALL, a cryptic t(7;11)(q35;q24) in association with a t(1;14)(p32;q32) in a patient with T-ALL and two translocations possibly involving the same 6q26 region on the distal end of the long arm of chromosome 6. Further FISH analysis on the t(7;11) indicated rearrangement of the TCRB locus at 7q35 suggesting that this t(7;11) leads to overexpression of an as yet unidentified gene at 11q24. This observation also triggered further screening for TCRB rearrangements in T-ALL. FISH analysis of the t(14;20) with an IGH locus-specific probe provided evidence for an unusual rearrangement of the IGH gene, in the variable gene segment region. Finally, we also observed cryptic insertions of AF4 and ETV6 in combination with complex rearrangements, leading to MLL/AF4 and ETV6/RUNX1 gene fusions., Interpretation and Conclusions: This study underscores the importance and power of M-FISH analysis in unraveling complex karyotypes and identifying cryptic chromosomal rearrangements. It also sheds some light on the implication of cryptic TCRB rearrangements in T-ALL.
- Published
- 2005
50. Do B-cell chronic lymphocytic leukemia patients with Ig VH3-21 genes constitute a new subset of chronic lymphocytic leukemia?
- Author
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Nollet F, Cauwelier B, Billiet J, Selleslag D, Van Hoof A, Louwagie A, and Criel A
- Subjects
- Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Leukemia, Lymphocytic, Chronic, B-Cell classification, Mutation, Genes, Immunoglobulin, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Published
- 2002
- Full Text
- View/download PDF
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