Search

Your search keyword '"Sandberg, Yorick"' showing total 131 results
Start Over Author "Sandberg, Yorick" Search Limiters Available in Library Collection
131 results on '"Sandberg, Yorick"'

1. A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

Author

de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G. G. M., Mous, Rogier, Vermaat, Joost S. P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, and Chamuleau, Martine E. D.

Published
2023
Full Text
View/download PDF

2. The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine:A Crossover Pharmacokinetic Study

Author

Guchelaar, Niels A. D., Buck, Stefan A. J., van Doorn, Leni, Hussaarts, Koen G. A. M., Sandberg, Yorick, van der Padt-pruijsten, Annemieke, van Alphen, Robbert J., Poppe-Manenschijn, Laura, Vleut, Isolde, de Bruijn, Peter, van Leeuwen, Roelof W. F., Mostert, Bianca, Eskens, Ferry A. L. M., Oomen-de Hoop, Esther, Koolen, Stijn L. W., Mathijssen, Ron H. J., Guchelaar, Niels A. D., Buck, Stefan A. J., van Doorn, Leni, Hussaarts, Koen G. A. M., Sandberg, Yorick, van der Padt-pruijsten, Annemieke, van Alphen, Robbert J., Poppe-Manenschijn, Laura, Vleut, Isolde, de Bruijn, Peter, van Leeuwen, Roelof W. F., Mostert, Bianca, Eskens, Ferry A. L. M., Oomen-de Hoop, Esther, Koolen, Stijn L. W., and Mathijssen, Ron H. J.

Abstract

Background and Objectives: Trifluridine/tipiracil, registered for the treatment of patients with metastatic gastric and colorectal cancer, is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein 1 (MATE1), which raises the potential for drug–drug interactions with other OCT2/MATE1 modulators. Therefore, we prospectively examined the effect of an OCT2/MATE1 inhibitor (cimetidine) and substrate (metformin) on the pharmacokinetics of trifluridine. Methods: In this three-phase crossover study, patients with metastatic colorectal or gastric cancer were sequentially treated with trifluridine/tipiracil alone (phase A), trifluridine/tipiracil concomitant with metformin (phase B) and trifluridine/tipiracil concomitant with cimetidine (phase C). The primary endpoint was the relative difference in exposure of trifluridine assessed by the area under the curve from timepoint zero to infinity. A > 30% change in exposure was considered clinically relevant. A p-value of < 0.025 was considered significant because of a Bonferroni correction. Results: Eighteen patients were included in the analysis. Metformin did not significantly alter the exposure to trifluridine (− 12.6%; 97.5% confidence interval − 25.0, 1.8; p = 0.045). Cimetidine did alter the exposure to trifluridine significantly (+ 18.0%; 97.5% confidence interval 4.5, 33.3; p = 0.004), but this increase did not meet our threshold for clinical relevance. Metformin trough concentrations were not influenced by trifluridine/tipiracil. Conclusions: Our result suggests that the OCT2/MATE1 modulators cimetidine and metformin can be co-administered with trifluridine/tipiracil without clinically relevant effects on drug exposure. Clinical Trial Registration: NL8067 (registered 04-10-2019).

Published
2024

6. Soft tissue lesion of the oral cavity

Author

Overweel, F. P., Rutgers, Robert, Budel, Leo M., Sandberg, Yorick, Overweel, F. P., Rutgers, Robert, Budel, Leo M., and Sandberg, Yorick

Published
2023

7. A non-randomized risk-adjusted comparison of lenalidomide + R-CHOP versus R-CHOP for MYC-rearranged DLBCL patients

Author

MS Hematologie, Cancer, Infection & Immunity, de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G.G.M., Mous, Rogier, Vermaat, Joost S.P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, Chamuleau, Martine E.D., MS Hematologie, Cancer, Infection & Immunity, de Jonge, A. Vera, van Werkhoven, Erik, Dinmohamed, Avinash G., Nijland, Marcel, Zwinderman, Aeilko H., Bossuyt, Patrick M., Veldhuis, Martine S., Rutten, Emma G.G.M., Mous, Rogier, Vermaat, Joost S.P., Sandberg, Yorick, de Jongh, Eva, Bilgin, Yavuz M., Boersma, Rinske, Koene, Harry, Kersten, Marie José, de Jong, Daphne, and Chamuleau, Martine E.D.

Published
2023

8. Immune Profiling of Double and Triple Hit High Grade B Cell Lymphoma Patients Treated with DA-EPOCH Reveals Activation of T Cells and Reduced T Cell Exhaustion

Author

de Jonge, A.Vera, primary, Duetz, Carolien, additional, Bruins, Wassilis S.C., additional, van Werkhoven, Erik D., additional, Nijland, Marcel, additional, Van Der Poel, Marjolein W.M., additional, de Heer, Koen, additional, Klerk, Clara P.W., additional, Sandberg, Yorick, additional, Fijnheer, Rob, additional, Mutseaers, Pim, additional, Issa, Djamila E., additional, Böhmer, Lara H., additional, Van Kampen, Roel J.W., additional, Visser, Otto J., additional, de Jong, Daphne, additional, Zijlstra, Josée M., additional, Mutis, Tuna, additional, and Chamuleau, Martine E.D., additional

Published
2022
Full Text
View/download PDF

9. Plasma Extracellular Vesicle-Associated microRNAs for Early Response Prediction in Patients with High-Grade B-Cell Lymphoma

Author

Wang, Steven, primary, Drees, Esther E.E., additional, Gómez-Martín, Cristina, additional, De Jonge, A., additional, van Eijndhoven, Monique, additional, Groenewegen, Nils, additional, Veldt-Verkuijlen, Sandra, additional, Nijland, Marcel, additional, Van Der Poel, Marjolein W.M., additional, Sandberg, Yorick, additional, van Rijn, Rozemarijn, additional, Mutsaers, Pim, additional, Vergote, Vibeke K.J., additional, Kersten, Marie José, additional, Bilgin, Yavuz M., additional, Stevens, Wendy B.C., additional, Durian, Marc, additional, Snijders, Tjeerd J.F., additional, de Jong, Daphne, additional, Zijlstra, Josée M., additional, Chamuleau, Martine E.D., additional, and Pegtel, Dirk Michiel, additional

Published
2022
Full Text
View/download PDF

10. A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC-Rearranged DLBCL Patients

Author

de Jonge, A. Vera, primary, van Werkhoven, Erik D., additional, Dinmohamed, Avinash G., additional, Nijland, Marcel, additional, Zwinderman, Aeilko H., additional, Bossuyt, Patrick M., additional, Veldhuis, Martine S., additional, Rutten, Emma G.G.M., additional, Mous, Rogier, additional, Vermaat, Joost S.P., additional, Sandberg, Yorick, additional, de Jongh, Eva, additional, Bilgin, Yavuz M., additional, Boersma, Rinske, additional, Koene, Harry R., additional, Kersten, Marie Jose, additional, de Jong, Daphne, additional, and Chamuleau, Martine E.D., additional

Published
2022
Full Text
View/download PDF

11. High Grade B Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements Treated with DA-EPOCH-R Induction and Nivolumab Consolidation Treatment: Interim Results of the HOVON-152 Phase II Trial

Author

de Jonge, A. Vera, primary, van Werkhoven, Erik D., additional, Nijland, Marcel, additional, de Heer, Koen, additional, Van Der Poel, Marjolein W.M., additional, Sandberg, Yorick, additional, Klerk, Clara, additional, Drees, Esther E.E., additional, Roemer, Margaretha GM, additional, de Jong, Daphne, additional, Pegtel, D. Michiel, additional, van der Holt, Bronno, additional, Mutis, Tuna, additional, Zijlstra, Josée M, additional, Kersten, Marie José, additional, and Chamuleau, Martine E.D, additional

Published
2021
Full Text
View/download PDF

13. Generating human prostate cancer organoids from leukapheresis enriched circulating tumour cells

Author

Mout, Lisanne, van Dessel, Lisanne F., Kraan, Jaco, de Jong, Anouk C., Neves, Rui P.L., Erkens-Schulze, Sigrun, Beaufort, Corine M., Sieuwerts, Anieta M., van Riet, Job, Woo, Thomas L.C., de Wit, Ronald, Sleijfer, Stefan, Hamberg, Paul, Sandberg, Yorick, te Boekhorst, Peter A.W., van de Werken, Harmen J.G., Martens, John W.M., Stoecklein, Nikolas H., van Weerden, Wytske M., Lolkema, Martijn P., Mout, Lisanne, van Dessel, Lisanne F., Kraan, Jaco, de Jong, Anouk C., Neves, Rui P.L., Erkens-Schulze, Sigrun, Beaufort, Corine M., Sieuwerts, Anieta M., van Riet, Job, Woo, Thomas L.C., de Wit, Ronald, Sleijfer, Stefan, Hamberg, Paul, Sandberg, Yorick, te Boekhorst, Peter A.W., van de Werken, Harmen J.G., Martens, John W.M., Stoecklein, Nikolas H., van Weerden, Wytske M., and Lolkema, Martijn P.

Abstract

Background: Circulating tumour cell (CTC)–derived organoids have the potential to provide a powerful tool for personalised cancer therapy but are restrained by low CTC numbers provided by blood samples. Here, we used diagnostic leukapheresis (DLA) to enrich CTCs from patients with metastatic prostate cancer (mPCa) and explored whether organoids provide a platform for ex vivo treatment modelling. Methods: We prospectively screened 102 patients with mPCa and performed DLA in 40 patients with ≥5 CTCs/7.5 mL blood. We enriched CTCs from DLA using white blood cell (WBC) depletion alone or combined with EpCAM selection. The enriched CTC samples were cultured in 3D to obtain organoids and used for downstream analyses. Results: The DLA procedure resulted in a median yield of 5312 CTCs as compared with 22 CTCs in 7.5 mL of blood. Using WBC depletion, we recovered 46% of the CTCs, which reduced to 12% with subsequent EpCAM selection. From the isolated and enriched CTC samples, organoid expansion succeeded in 35%. Successful organoid cultures contained significantly higher CTC numbers at initiation. Moreover, we performed treatment modelling in one organoid cell line and identified substantial tumour heterogeneity in CTCs using single cell DNA sequencing. Conclusions: DLA is an efficient method to enrich CTCs, although the modest success rate of culturing CTCs precludes large scale clinical application. Our data do suggest that DLA and subsequent processing provides a rich source of viable tumour cells. Therefore, DLA offers a promising alternative to biopsy procedures to obtain sufficient number of tumour cells to study sequential samples in patients with mPCa. Trial registration number: NL6019.

Published
2021

14. DA-EPOCH-R for High Grade B-Cell Lymphoma Patients with MYC and BCL2 and/or BCL6 Rearrangements: Clinical Results of the Induction Phase of the HOVON-152 Trial

Author

de Jonge, A.Vera, Kersten, Marie José, van Werkhoven, Erik, van der Poel, Marjolein, de Heer, Koen, Klerk, Clara, Sandberg, Yorick, Van Rijn, Rozemarijn S, Fijnheer, Rob, Mutsaers, Pim, Vergote, Vibeke, Issa, Djamila, Beeker, Aart, Bilgin, Yavuz M., Böhmer, Lara H., Nieuwenhuizen, Laurens, Stevens, Wendy, van Kampen, Roel JW, Mous, Rogier, Durian, Marc, Snijders, Tjeerd, Vermaat, Joost S.P, Visser, Otto, Zijlstra, Josée M., Hofwegen, Henk, Zanders, Helma G.J.M., Fu, Liping P., De Jong, Daphne, Nijland, Marcel, and Chamuleau, Martine E.D.

Published
2023
Full Text
View/download PDF

17. Acquired haemophilia A after alemtuzumab therapy

Author

van der Zwan, Marieke, Leebeek, Frank W.G., Sandberg, Yorick, Kruip, Marieke J.H.A., Hesselink, Dennis A., van der Zwan, Marieke, Leebeek, Frank W.G., Sandberg, Yorick, Kruip, Marieke J.H.A., and Hesselink, Dennis A.

Published
2020

19. Abstract 3919: Liquid biopsy derived organoids as a potential platform for personalized cancer therapy in metastatic prostate cancer

Author

Mout, Lisanne, primary, van Dessel, Lisanne F., additional, Kraan, Jaco, additional, de Jong, Anouk C., additional, Neves, Rui P., additional, Erkens-Schulze, Sigrun, additional, Siewerts, Anieta M., additional, van Riet, Job, additional, de Wit, Ronald, additional, Sleijfer, Stefan, additional, Hamberg, Paul, additional, Sandberg, Yorick, additional, te Boekhorst, Peter A., additional, van de Werken, Harmen J., additional, Martens, John W., additional, Stoecklein, Nikolas H., additional, van Weerden, Wytske M., additional, and Lolkema, Martijn P., additional

Published
2020
Full Text
View/download PDF

22. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, Panagiotis, Mattsson, Mattias, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andreas, Sutton, Lesley Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J., Tzenou, Tatiana, Chu, Charles C., Veronese, Silvio, Mansouri, Larry, Smedby, Karin E., Giudicelli, Veronique, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U., Langerak, Anton W., Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Shanafelt, Tait, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Mattsson, Mattias, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andreas, Sutton, Lesley Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J., Tzenou, Tatiana, Chu, Charles C., Veronese, Silvio, Mansouri, Larry, Smedby, Karin E., Giudicelli, Veronique, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U., Langerak, Anton W., Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Shanafelt, Tait, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2018
Full Text
View/download PDF

23. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, Stamatopoulos, K, Baliakas, P, Mattsson, M, Hadzidimitriou, A, Minga, E, Agathangelidis, A, Sutton, LA, Scarfo, L, Davis, Z, Yan, XJ, Plevova, K, Sandberg, Yorick, Vojdeman, FJ, Tzenou, T, Chu, CC, Veronese, S, Mansouri, L, Smedby, KE, Giudicelli, V, Nguyen-Khac, F, Panagiotidis, P, Juliusson, G, Anagnostopoulos, A, Lefranc, MP, Trentin, L, Catherwood, M, Montillo, M, Niemann, CU, Langerak, Ton, Pospisilova, S, Stavroyianni, N, Chiorazzi, N, Oscier, D, Jelinek, DF, Shanafelt, T, Darzentas, N, Belessi, C, Davi, F, Ghia, P, Rosenquist, R, and Stamatopoulos, K

Published
2018

26. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Baliakas, Panagiotis, primary, Mattsson, Mattias, additional, Hadzidimitriou, Anastasia, additional, Minga, Eva, additional, Agathangelidis, Andreas, additional, Sutton, Lesley-Ann, additional, Scarfo, Lydia, additional, Davis, Zadie, additional, Yan, Xiao-Jie, additional, Plevova, Karla, additional, Sandberg, Yorick, additional, Vojdeman, Fie J., additional, Tzenou, Tatiana, additional, Chu, Charles C., additional, Veronese, Silvio, additional, Mansouri, Larry, additional, Smedby, Karin E, additional, Giudicelli, Véronique, additional, Nguyen-Khac, Florence, additional, Panagiotidis, Panagiotis, additional, Juliusson, Gunnar, additional, Anagnostopoulos, Achilles, additional, Lefranc, Marie-Paule, additional, Trentin, Livio, additional, Catherwood, Mark, additional, Montillo, Marco, additional, Niemann, Carsten U., additional, Langerak, Anton W., additional, Pospisilova, Sarka, additional, Stavroyianni, Niki, additional, Chiorazzi, Nicholas, additional, Oscier, David, additional, Jelinek, Diane F, additional, Shanafelt, Tait, additional, Darzentas, Nikos, additional, Belessi, Chrysoula, additional, Davi, Frederic, additional, Ghia, Paolo, additional, Rosenquist, Richard, additional, and Stamatopoulos, Kostas, additional

Published
2017
Full Text
View/download PDF

27. Dysregulated signaling, proliferation and apoptosis impact on the pathogenesis of TCRγδ+ T cell large granular lymphocyte leukemia

Author

Kallemeijn, Martine J., Ridder, Dick, de, Schilperoord-Vermeulen, Joyce, Klift, Michèle Y., van der, Sandberg, Yorick, Dongen, Jacques J.M., van, Langerak, Anton W., Kallemeijn, Martine J., Ridder, Dick, de, Schilperoord-Vermeulen, Joyce, Klift, Michèle Y., van der, Sandberg, Yorick, Dongen, Jacques J.M., van, and Langerak, Anton W.

Abstract

TCRγδ+ T-LGL leukemia is a rare form of chronic mature T cell disorders in elderly, which is generally characterized by a persistently enlarged CD3+CD57+TCRγδ+ large granular lymphocyte population in the peripheral blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most patients being largely asymptomatic, although neutropenia, fatigue and B symptoms and underlying diseases such as autoimmune diseases or malignancies are also often observed. The etiology of TCRγδ+ T-LGL proliferations is largely unknown. Here, we aimed to investigate underlying molecular mechanisms of these rare proliferations by performing gene expression profiling of TCRγδ+ T-LGL versus normal TCRγδ+ T cell subsets. From our initial microarray dataset we observed that TCRγδ+ TLGL leukemia forms a separate group when compared with different healthy control TCRγδ + T cell subsets, correlating best with the healthy TemRA subset. The lowest correlation was seen with the naive subset. Based on specific comparison between healthy control cells and TCRγδ+ T-LGL leukemia cells we observed up-regulation of survival, proliferation and hematopoietic system related genes, with a remarkable down-regulation of apoptotic pathway genes. RQ-PCR validation of important genes representative for the dataset, including apoptosis (XIAP, CASP1, BCLAF1 and CFLAR), proliferation/development (ID3) and inflammation (CD28, CCR7, CX3CR1 and IFNG) processes largely confirmed the dysregulation in proliferation and apoptosis. Based on these expression data we conclude that TCRγδ+ T-LGL leukemia is likely the result of an underlying aberrant molecular mechanisms leading to increased proliferation and reduced apoptosis.

Published
2017

28. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors : Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Vlahavas, Ioannis, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Vlahavas, Ioannis, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Abstract

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.

Published
2017
Full Text
View/download PDF

29. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations

Author

Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Tsanousa, Athina, Scarfò, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C., Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E., Pedersen, Lone Bredo, Moreno, Denis, Van Lom, Kirsten, Giudicelli, Véronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H., Langerak, Anton W., Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2015
Full Text
View/download PDF

30. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Xochelli, Aliki, primary, Baliakas, Panagiotis, additional, Kavakiotis, Ioannis, additional, Agathangelidis, Andreas, additional, Sutton, Lesley-Ann, additional, Minga, Eva, additional, Ntoufa, Stavroula, additional, Tausch, Eugen, additional, Yan, Xiao-Jie, additional, Shanafelt, Tait, additional, Plevova, Karla, additional, Boudjogra, Myriam, additional, Rossi, Davide, additional, Davis, Zadie, additional, Navarro, Alba, additional, Sandberg, Yorick, additional, Vojdeman, Fie Juhl, additional, Scarfo, Lydia, additional, Stavroyianni, Niki, additional, Sudarikov, Andrey, additional, Veronese, Silvio, additional, Tzenou, Tatiana, additional, Karan-Djurasevic, Teodora, additional, Catherwood, Mark, additional, Kienle, Dirk, additional, Chatzouli, Maria, additional, Facco, Monica, additional, Bahlo, Jasmin, additional, Pott, Christiane, additional, Pedersen, Lone Bredo, additional, Mansouri, Larry, additional, Smedby, Karin E., additional, Chu, Charles C., additional, Giudicelli, Véronique, additional, Lefranc, Marie-Paule, additional, Panagiotidis, Panagiotis, additional, Juliusson, Gunnar, additional, Anagnostopoulos, Achilles, additional, Vlahavas, Ioannis, additional, Antic, Darko, additional, Trentin, Livio, additional, Montillo, Marco, additional, Niemann, Carsten, additional, Döhner, Hartmut, additional, Langerak, Anton W., additional, Pospisilova, Sarka, additional, Hallek, Michael, additional, Campo, Elias, additional, Chiorazzi, Nicholas, additional, Maglaveras, Nikos, additional, Oscier, David, additional, Gaidano, Gianluca, additional, Jelinek, Diane F., additional, Stilgenbauer, Stephan, additional, Chouvarda, Ioanna, additional, Darzentas, Nikos, additional, Belessi, Chrysoula, additional, Davi, Frederic, additional, Hadzidimitriou, Anastasia, additional, Rosenquist, Richard, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2017
Full Text
View/download PDF

32. CLL with Mutated IGHV4-34 Antigen Receptors Is Clinically Heterogeneous : Antigen Receptor Stereotypy Makes the Difference

Author

Xochelli, Aliki, Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Tausch, Eugen, Yan, Xiao J., Shanafelt, Tait D., Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey B., Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Dohner, Hartmut, Langerak, Anton W., Darzentas, Nikos, Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Oscier, David, Gaidano, Gianluca, Belessi, Chrysoula, Jelinek, Diane F., Stilgenbauer, Stephan, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Xochelli, Aliki, Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Tausch, Eugen, Yan, Xiao J., Shanafelt, Tait D., Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey B., Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Dohner, Hartmut, Langerak, Anton W., Darzentas, Nikos, Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Oscier, David, Gaidano, Gianluca, Belessi, Chrysoula, Jelinek, Diane F., Stilgenbauer, Stephan, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2015

33. Not all IGHV3-21 chronic lymphocytic leukemias are equal:prognostic considerations

Author

Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Tsanousa, Athina, Scarfò, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C, Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E, Pedersen, Lone Bredo, Moreno, Denis, Van Lom, Kirsten, Giudicelli, Véronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H, Langerak, Anton W, Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Tsanousa, Athina, Scarfò, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C, Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E, Pedersen, Lone Bredo, Moreno, Denis, Van Lom, Kirsten, Giudicelli, Véronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H, Langerak, Anton W, Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Abstract

An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

Published
2015

34. Disseminated fusariosis

Author

Sandberg, Yorick, Clahsen - van Groningen, Marian, Ammatuna, Emanuele, Sandberg, Yorick, Clahsen - van Groningen, Marian, and Ammatuna, Emanuele

Published
2015

35. CLL with Mutated IGHV4-34 Antigen Receptors Is Clinically Heterogeneous: Antigen Receptor Stereotypy Makes the Difference

Author

Xochelli, Aliki, primary, Baliakas, Panagiotis, additional, Agathangelidis, Andreas, additional, Hadzidimitriou, Anastasia, additional, Sutton, Lesley-Ann, additional, Minga, Eva, additional, Tausch, Eugen, additional, Yan, Xiao J., additional, Shanafelt, Tait D., additional, Plevova, Karla, additional, Boudjogra, Myriam, additional, Rossi, Davide, additional, Davis, Zadie, additional, Navarro, Alba, additional, Sandberg, Yorick, additional, Vojdeman, Fie Juhl, additional, Scarfo, Lydia, additional, Stavroyianni, Niki, additional, Sudarikov, Andrey B., additional, Veronese, Silvio, additional, Tzenou, Tatiana, additional, Karan-Djurasevic, Teodora, additional, Catherwood, Mark, additional, Kienle, Dirk, additional, Chatzouli, Maria, additional, Facco, Monica, additional, Bahlo, Jasmin, additional, Pedersen, Lone Bredo, additional, Mansouri, Larry, additional, Smedby, Karin E, additional, Chu, Charles C, additional, Giudicelli, Véronique, additional, Lefranc, Marie-Paule, additional, Panagiotidis, Panagiotis, additional, Juliusson, Gunnar, additional, Anagnostopoulos, Achilles, additional, Antic, Darko, additional, Trentin, Livio, additional, Montillo, Marco, additional, Niemann, Carsten, additional, Döhner, Hartmut, additional, Langerak, Anton W., additional, Darzentas, Nikos, additional, Pospisilova, Sarka, additional, Hallek, Michael, additional, Campo, Elias, additional, Chiorazzi, Nicholas, additional, Oscier, David, additional, Gaidano, Gianluca, additional, Belessi, Chrysoula, additional, Jelinek, Diane F., additional, Stilgenbauer, Stephan, additional, Davi, Frederic, additional, Rosenquist, Richard, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2015
Full Text
View/download PDF

36. Dynamic Frailty Status Enables Better Prediction of Survival Probability - Results of the HOVON 143 Study

Author

Smits, Febe, Groen, Kaz, Levin, Mark-David, Stege, Claudia, Van Kampen, Roel JW, Van Der Spek, Ellen, Bilgin, Yavuz M, Thielen, Noortje, Nijhof, Inger S., Ludwig, Inge, De Waal, Esther G.M., Sandberg, Yorick, Kentos, Alain, Timmers, Gert Jan, Regelink, Josien C, Westerman, Matthijs, de Heer, Koen, Vekemans, Marie Christiane, Durdu-Rayman, Nazik, Graauw, Nicole de, Seefat, Maarten R., van de Donk, Niels WCJ, Ypma, Paula F, Nasserinejad, Kazem, and Zweegman, Sonja

Abstract

Introduction

Published
2023
Full Text
View/download PDF

38. Clinical Impact of Stereotyped Antigen Receptors in Chronic Lymphocytic Leukemia

Author

Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Evangelia, Agathangelidis, Andreas, Tsanousa, Athina, Scarfo, Lydia, Davis, Zadie, Yan, Joy, Shanafelt, Tait D., Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjoghra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C., Veronese, Silvio, Gardiner, Anne Catherine, Mansouri, Larry, Smedby, Karin E., Pedersen, Lone, Moreno, Denis, van Lom, Kirsten, Giudicelli, Veronique, Francova, Hana, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H., Langerak, Anton W., Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Evangelia, Agathangelidis, Andreas, Tsanousa, Athina, Scarfo, Lydia, Davis, Zadie, Yan, Joy, Shanafelt, Tait D., Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjoghra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C., Veronese, Silvio, Gardiner, Anne Catherine, Mansouri, Larry, Smedby, Karin E., Pedersen, Lone, Moreno, Denis, van Lom, Kirsten, Giudicelli, Veronique, Francova, Hana, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H., Langerak, Anton W., Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2014

39. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia : a retrospective multicentre study

Author

Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Agathangelidis, Andreas, Nichelatti, Michele, Tsanousa, Athina, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C., Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E., Pedersen, Lone Bredo, van Lom, Kirsten, Giudicelli, Veronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H., Langerak, Anton W., Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Rosenquist Barndell, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, Agathangelidis, Andreas, Nichelatti, Michele, Tsanousa, Athina, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie Juhl, Boudjogra, Myriam, Tzenou, Tatiana, Chatzouli, Maria, Chu, Charles C., Veronese, Silvio, Gardiner, Anne, Mansouri, Larry, Smedby, Karin E., Pedersen, Lone Bredo, van Lom, Kirsten, Giudicelli, Veronique, Francova, Hana Skuhrova, Nguyen-Khac, Florence, Panagiotidis, Panagiotis, Juliusson, Gunnar, Angelis, Lefteris, Anagnostopoulos, Achilles, Lefranc, Marie-Paule, Facco, Monica, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Geisler, Christian H., Langerak, Anton W., Pospisilova, Sarka, Chiorazzi, Nicholas, Oscier, David, Jelinek, Diane F., Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Rosenquist Barndell, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Abstract

Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively accoun

Published
2014
Full Text
View/download PDF

40. Lack of common TCRA and TCRB clonotypes in CD8(+)/TCR alpha beta(+) T-cell large granular lymphocyte leukemia: a review on the role of antigenic selection in the immunopathogenesis of CD8(+) T-LGL

Author

Sandberg, Yorick, Kallemeijn, Martine, Dik, Wim, Tielemans, Dennis, Tettero, Ingrid, Mol, Ellen, Szczepanski, Tomek, Pol, Y (Y.), Darzentas, N, Dongen, Jacques, Langerak, Ton, Sandberg, Yorick, Kallemeijn, Martine, Dik, Wim, Tielemans, Dennis, Tettero, Ingrid, Mol, Ellen, Szczepanski, Tomek, Pol, Y (Y.), Darzentas, N, Dongen, Jacques, and Langerak, Ton

Abstract

Clonal CD8(+)/T-cell receptor (TCR)alpha beta(+) T-cell large granular lymphocyte (T-LGL) proliferations constitute the most common subtype of T-LGL leukemia. Although the etiology of T-LGL leukemia is largely unknown, it has been hypothesized that chronic antigenic stimulation contributes to the pathogenesis of this disorder. In the present study, we explored the association between expanded TCR-V beta and TCR-V alpha clonotypes in a cohort of 26 CD8(+)/TCR alpha beta(+) T-LGL leukemia patients, in conjunction with the HLA-ABC genotype, to find indications for common antigenic stimuli. In addition, we applied purpose-built sophisticated computational tools for an in-depth evaluation of clustering of TCR beta (TCRB) complementarity determining region 3 (CDR3) amino-acid LGL clonotypes. We observed a lack of clear TCRA and TCRB CDR3 homology in CD8(+)/TCR alpha beta(+) T-LGL, with only low level similarity between small numbers of cases. This is in strong contrast to the homology that is seen in CD4(+)/TCR alpha beta(+) T-LGL and TCR gamma delta(+) T-LGL and thus underlines the idea that the LGL types have different etiopathogenesis. The heterogeneity of clonal CD8(+)/TCR alpha beta(+) T-LGL proliferations might in fact suggest that multiple pathogens or autoantigens are involved.

Published
2014

41. Clinical Impact of Stereotyped Antigen Receptors in Chronic Lymphocytic Leukemia

Author

Baliakas, Panagiotis, primary, Hadzidimitriou, Anastasia, additional, Sutton, Lesley-Ann, additional, Minga, Evangelia, additional, Agathangelidis, Andreas, additional, Tsanousa, Athina, additional, Scarfo, Lydia, additional, Davis, Zadie, additional, Yan, Joy, additional, Shanafelt, Tait D., additional, Plevova, Karla, additional, Sandberg, Yorick, additional, Vojdeman, Fie Juhl, additional, Boudjoghra, Myriam, additional, Tzenou, Tatiana, additional, Chatzouli, Maria, additional, Chu, Charles C., additional, Veronese, Silvio, additional, Gardiner, Anne Catherine, additional, Mansouri, Larry, additional, Smedby, Karin E, additional, Pedersen, Lone, additional, Moreno, Denis, additional, van Lom, Kirsten, additional, Giudicelli, Veronique, additional, Francova, Hana, additional, Nguyen-Khac, Florence, additional, Panagiotidis, Panagiotis, additional, Juliusson, Gunnar, additional, Angelis, Lefteris, additional, Anagnostopoulos, Achilles, additional, Lefranc, Marie-Paule, additional, Facco, Monica, additional, Trentin, Livio, additional, Catherwood, Mark, additional, Montillo, Marco, additional, Geisler, Christian H, additional, Langerak, Anton W, additional, Pospisilova, Sarka, additional, Chiorazzi, Nicholas, additional, Oscier, David, additional, Jelinek, Diane F., additional, Darzentas, Nikos, additional, Belessi, Chrysoula, additional, Davi, Frederic, additional, Rosenquist, Richard, additional, Ghia, Paolo, additional, and Stamatopoulos, Kostas, additional

Published
2014
Full Text
View/download PDF

45. Monoclonal TCR-Vβ13.1+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin

Author

Garrido, Pilar, primary, Ruiz-Cabello, Francisco, additional, Bárcena, Paloma, additional, Sandberg, Yorick, additional, Cantón, Julia, additional, Lima, Margarida, additional, Balanzategui, Ana, additional, González, Marcos, additional, López-Nevot, Miguel Angel, additional, Langerak, Anton W., additional, García-Montero, Andrés C., additional, Almeida, Julia, additional, and Orfao, Alberto, additional

Published
2007
Full Text
View/download PDF

46. Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dimT-LGL lymphocytosis recognize hCMV antigens

Author

Rodríguez-Caballero, Arancha, García-Montero, Andrés C., Bárcena, Paloma, Almeida, Julia, Ruiz-Cabello, Francisco, Tabernero, Maria Dolores, Garrido, Pilar, Muñoz-Criado, Santiago, Sandberg, Yorick, Langerak, Anton W., González, Marcos, Balanzategui, Ana, and Orfao, Alberto

Abstract

Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal T-cell receptor (TCR)–αβ+/CD4+/NKa+/CD8−/+dimT-large granular lymphocyte (LGL) lymphocytosis. Because healthy persons show (oligo)clonal expansions of human cytomegalovirus (hCMV)–specific TCRVβ+/CD4+/cytotoxic/memory T cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+T-LGL. Peripheral blood samples from patients with monoclonal TCR-αβ+/CD4+T-LGL lymphocytosis and other T-chronic lymphoproliferative disorders were evaluated for the specific functional response against hCMV and hEBV whole lysates as well as the “MQLIPDDYSNTHSTRYVTVK” hCMV peptide, which is specifically loaded in HLA-DRB1*0701 molecules. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile analysis. Patients with TCR-αβ+/CD4+T-LGL displayed a strong and characteristic hCMV-specific functional response, reproduced by the hCMV peptide in a subset of HLA-DRB1*0701+patients bearing TCRVβ13.1+clonal T cells. Gene expression profile showed that the hCMV-induced response affects genes involved in inflammatory and immune responses, cell cycle progression, resistance to apoptosis, and genetic instability. This is the first study providing evidence for the involvement of hCMV in the ontogeny of CD4+T-LGL, emerging as a model disorder to determine the potential implications of quite a focused CD4+/cytotoxic immune response.

Published
2008
Full Text
View/download PDF

47. Monoclonal TCR-Vβ13.1+/CD4+/NKa+/CD8−/+dimT-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin

Author

Garrido, Pilar, Ruiz-Cabello, Francisco, Bárcena, Paloma, Sandberg, Yorick, Cantón, Julia, Lima, Margarida, Balanzategui, Ana, González, Marcos, López-Nevot, Miguel Angel, Langerak, Anton W., García-Montero, Andrés C., Almeida, Julia, and Orfao, Alberto

Abstract

Monoclonal TCRαβ+/CD4+T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-Vβ repertoire. In the present study we explored the potential association between the expanded TCR-Vβ families, the CDR3 sequences of the TCR-Vβ gene, and the HLA genotype of patients with monoclonal TCRαβ+/CD4+T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCRαβ+/CD4+T-LGL lymphocytosis (15 TCR-Vβ13.1 versus 21 non–TCR-Vβ13.1) were selected. For each patient, both the HLA (class I and II) genotype and the DNA sequences of the VDJ-rearranged TCR-Vβ were analyzed. Our results show a clear association between the TCR-Vβ repertoire and the HLA genotype, all TCR-Vβ13.1+cases being HLA-DRB1*0701 (P= .004). Interestingly, the HLA-DR7/TCR-Vβ13.1–restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR arising from the use of common TCR-Vβ gene segments, which shared (1) unique CDR3 structural features with a constantly short length, (2) similar combinatorial gene rearrangements with frequent usage of the Jβ1.1 gene, and (3) a homolog consensus protein sequence at recombination junctions. Overall, these findings strongly support the existence of a common antigen-driven origin for monoclonal CD4+T-LGL lymphocytosis, with the identification of the exact peptides presented to the expanded T cells deserving further investigations.

Published
2007
Full Text
View/download PDF

48. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

Véronique Giudicelli, Lesley-Ann Sutton, Panagiotis Baliakas, Anastasia Hadzidimitriou, David Oscier, Kostas Stamatopoulos, Michael Hallek, Eugen Tausch, Marco Montillo, Achilles Anagnostopoulos, Elias Campo, Yorick Sandberg, Silvio Veronese, Šárka Pospíšilová, Dirk Kienle, Karin E. Smedby, Xiao-Jie Yan, Lydia Scarfò, Andreas Agathangelidis, Nikos Darzentas, Richard Rosenquist, Stavroula Ntoufa, Larry Mansouri, Darko Antic, Niki Stavroyianni, Aliki Xochelli, Tait D. Shanafelt, Tatiana Tzenou, Andrey Sudarikov, Charles C. Chu, Anton W. Langerak, Marie-Paule Lefranc, Nicholas Chiorazzi, Eva Minga, Carsten Utoft Niemann, Ioanna Chouvarda, Nikos Maglaveras, Gianluca Gaidano, Maria Chatzouli, Karla Plevová, Mark Catherwood, Hartmut Döhner, Chrysoula Belessi, Myriam Boudjogra, Zadie Davis, Ioannis Kavakiotis, Gunnar Juliusson, Livio Trentin, Frederic Davi, Davide Rossi, Jasmin Bahlo, Diane F. Jelinek, Monica Facco, Christiane Pott, Lone Bredo Pedersen, Panagiotis Panagiotidis, Fie Juhl Vojdeman, Stephan Stilgenbauer, Teodora Karan-Djurasevic, Alba Navarro, Paolo Ghia, Ioannis Vlahavas, Immunology, Xochelli, Aliki, Baliakas, Panagioti, Kavakiotis, Ioanni, Agathangelidis, Andrea, Sutton, Lesley-Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E, Chu, Charles C, Giudicelli, Véronique, Lefranc, Marie-Paule, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Vlahavas, Ioanni, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Döhner, Hartmut, Langerak, Anton W, Pospisilova, Sarka, Hallek, Michael, Campo, Elia, Chiorazzi, Nichola, Maglaveras, Niko, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F, Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas

Subjects
Male, 0301 basic medicine, Cancer Research, Chronic lymphocytic leukemia, B-cell receptor, Immunoglobulin Variable Region, Somatic hypermutation, Immunogenetics, Disease, Biology, 03 medical and health sciences, hemic and lymphatic diseases, medicine, Humans, Amino Acid Sequence, breakpoint cluster region, Chronic Lymphocytic Leukemia B cell receptor BCR Immunoglobulin, medicine.disease, ADP-ribosyl Cyclase 1, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Gene Expression Regulation, Neoplastic, Leukemia, 030104 developmental biology, Oncology, Immunology, biology.protein, Female, Somatic Hypermutation, Immunoglobulin, Antibody, Immunoglobulin Heavy Chains
Abstract

Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.

Published
2017

49. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy

Author

Tatiana Tzenou, Richard Rosenquist, Marie-Paule Lefranc, Karla Plevová, Charles C. Chu, Yorick Sandberg, Gunnar Juliusson, Véronique Giudicelli, Livio Trentin, Mark Catherwood, Frederic Davi, Šárka Pospíšilová, Xiao-Jie Yan, Silvio Veronese, Lesley-Ann Sutton, Carsten Utoft Niemann, Nikos Darzentas, Kostas Stamatopoulos, Achilles Anagnostopoulos, Diane F. Jelinek, David Oscier, Mattias Mattsson, Nicholas Chiorazzi, Karin E. Smedby, Panagiotis Panagiotidis, Chrysoula Belessi, Florence Nguyen-Khac, Marco Montillo, Eva Minga, Paolo Ghia, Anton W. Langerak, Lydia Scarfò, Andreas Agathangelidis, Tait D. Shanafelt, Panagiotis Baliakas, Niki Stavroyianni, Larry Mansouri, Anastasia Hadzidimitriou, Zadie Davis, Fie Juhl Vojdeman, Uppsala Universitet [Uppsala], Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Department of Hematology [Uppsala], Università Vita-Salute San Raffaele, Milan, Italy., Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Università Vita e Salute, San Raffaele, Milano, Italy, Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., The Feinstein Institute for Medical Research, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hematology and Transplantation, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Venetian Institute Molecular Medicine (VIMM), Department of Hemato-Oncology, Belfast City Hospital, Belfast, UK, University Hospital Brno, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Immunology, Mayo Clinic, Rochester, MV, USA, Mayo Clinic [Rochester], Hematology Department, Nikea General Hospital, Piraeus, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden., Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Institute of Applied Biosciences, Thessaloniki, Greece., Department of Immunology, Baliakas, Panagioti, Mattsson, Mattia, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andrea, Sutton, Lesley-Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J, Tzenou, Tatiana, Chu, Charles C, Veronese, Silvio, Mansouri, Larry, Smedby, Karin E, Giudicelli, Véronique, Nguyen-Khac, Florence, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U, Langerak, Anton W, Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nichola, Oscier, David, Jelinek, Diane F, Shanafelt, Tait, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, and Immunology

Subjects
Adult, Male, chemorefractorine, Oncology, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Young Adult, 03 medical and health sciences, 0302 clinical medicine, Drug Therapy, Chemoimmunotherapy, Internal medicine, medicine, Humans, Chronic Lymphocytic Leukemia, [INFO]Computer Science [cs], stereotyped subsets, Online Only Articles, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, [SDV.GEN]Life Sciences [q-bio]/Genetics, Hematology, business.industry, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, Survival Rate, Leukemia, 030220 oncology & carcinogenesis, Female, Rituximab, Immunotherapy, business, 030215 immunology, medicine.drug
Abstract

The overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) has improved over the last decades mainly due to advances in the understanding of the disease biology and the introduction of novel therapeutic approaches(1). In the present retrospective study we investigated trends in OS in subgroups of cases defined by genetic and immunogenetic features aiming at addressing the question whether advances in chemoimmunotherapy had a uniform impact across all CLL patients. We found that such advances have translated into prolonged OS in all prognostic subgroups examined except those carrying TP53 abnormalities, as expected, but also those assigned to stereotyped subsets #1 and #2, that are generally devoid of such gene aberrations. This latter finding, reported here for the first time, indicates the need for alternative treatment options for these patients.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results