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Start Over Author "Hadzidimitriou, A" Publisher uppsala universitet, science for life laboratory, scilifelab
25 results on '"Hadzidimitriou, A"'

1. Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Author

Zadie Davis, Richard Rosenquist, Chrysoula Belessi, Panagiotis Baliakas, Niki Stavroyianni, Theodoros Moysiadis, Elias Campo, Julio Delgado, Šárka Pospíšilová, Kostas Stamatopoulos, Marta Larrayoz, Davide Rossi, Jonathan C. Strefford, Larry Mansouri, Achilles Anagnostopoulos, Mattias Mattsson, Karin E. Smedby, Diego Cortese, Anastasia Hadzidimitriou, Lesley-Ann Sutton, Neus Villamor, David Oscier, Alba Navarro, Jana Kotašková, Evangelia Stalika, Gianluca Gaidano, Karla Plevová, Mark Catherwood, Gunnar Juliusson, Paolo Ghia, Sabine Jeromin, Oonagh Sheehy, Lydia Scarfò, Andreas Agathangelidis, Emma Young, Helen Parker, Eva Minga, Aliki Xochelli, Claudia Haferlach, Baliakas, Panagioti, Moysiadis, Theodoro, Hadzidimitriou, Anastasia, Xochelli, Aliki, Jeromin, Sabine, Agathangelidis, Andrea, Mattsson, Mattia, Sutton, Lesley-Ann, Minga, Eva, Scarfò, Lydia, Rossi, Davide, Davis, Zadie, Villamor, Neu, Parker, Helen, Kotaskova, Jana, Stalika, Evangelia, Plevova, Karla, Mansouri, Larry, Cortese, Diego, Navarro, Alba, Delgado, Julio, Larrayoz, Marta, Young, Emma, Anagnostopoulos, Achille, Smedby, Karin E., Juliusson, Gunnar, Sheehy, Oonagh, Catherwood, Mark, Strefford, Jonathan C., Stavroyianni, Niki, Belessi, Chrysoula, Pospisilova, Sarka, Oscier, David, Gaidano, Gianluca, Campo, Elia, Haferlach, Claudia, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, and Universitat de Barcelona

Subjects
Male, Oncology, medicine.medical_specialty, Pronòstic mèdic, Chronic lymphocytic leukemia, Somatic hypermutation, Relative weight, Kaplan-Meier Estimate, Immunogenetics, Article, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Biomarkers, Tumor, medicine, Humans, Chronic Lymphocytic Leukemia, Leucèmia limfocítica crònica, Hematologi, Aged, Neoplasm Staging, 030304 developmental biology, Aged, 80 and over, Chromosome Aberrations, 0303 health sciences, Hematology, biology, business.industry, medicine.disease, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, Mutation, biology.protein, Female, Disease Susceptibility, Antibody, business, Trisomy
Abstract

Chronic lymphocytic leukemia patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinicobiological differences. Considering this, we assessed prognosis separately within mutated and unmutated chronic lymphocytic leukemia in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet-A mutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at 5- and 10-years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet-A unmutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-trearment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage chronic lymphocytic leukemia patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in chronic lymphocytic leukemia.

Published
2019

2. Integrated epigenomic and transcriptomic analysis reveals TP63 as a novel player in clinically aggressive chronic lymphocytic leukemia

Author

Papakonstantinou, Nikos, Ntoufa, Stavroula, Tsagiopoulou, Maria, Moysiadis, Theodoros, Bhoi, Sujata, Malousi, Andigoni, Psomopoulos, Fotis, Mansouri, Larry, Laidou, Stamatia, Papazoglou, Despoina, Gounari, Maria, Pasentsis, Konstantinos, Plevova, Karla, Kuci-Emruli, Venera, Duran-Ferrer, Marti, Davis, Zadie, Ek, Sara, Rossi, Davide, Gaidano, Gianluca, Ritgen, Matthias, Oscier, David, Stavroyianni, Niki, Pospisilova, Sarka, Davi, Frederic, Ghia, Paolo, Hadzidimitriou, Anastasia, Belessi, Chrysoula, Martin-Subero, Jose, I, Pott, Christiane, Rosenquist, Richard, Stamatopoulos, Kostas, Papakonstantinou, Nikos, Ntoufa, Stavroula, Tsagiopoulou, Maria, Moysiadis, Theodoros, Bhoi, Sujata, Malousi, Andigoni, Psomopoulos, Fotis, Mansouri, Larry, Laidou, Stamatia, Papazoglou, Despoina, Gounari, Maria, Pasentsis, Konstantinos, Plevova, Karla, Kuci-Emruli, Venera, Duran-Ferrer, Marti, Davis, Zadie, Ek, Sara, Rossi, Davide, Gaidano, Gianluca, Ritgen, Matthias, Oscier, David, Stavroyianni, Niki, Pospisilova, Sarka, Davi, Frederic, Ghia, Paolo, Hadzidimitriou, Anastasia, Belessi, Chrysoula, Martin-Subero, Jose, I, Pott, Christiane, Rosenquist, Richard, and Stamatopoulos, Kostas

Abstract

Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on epigenomic signatures and their links with gene expression, particularly investigating genome-wide DNA methylation profiles in subsets #6 and #8 as well as other U-CLL cases not expressing stereotyped BcR IG. We found that subset #8 showed a distinctive DNA methylation profile compared to all other U-CLL cases, including subset #6. Integrated analysis of DNA methylation and gene expression revealed significant correlation for several genes, particularly highlighting a relevant role for the TP63 gene which was hypomethylated and overexpressed in subset #8. This observation was validated by quantitative PCR, which also revealed TP63 mRNA overexpression in additional nonsubset U-CLL cases. BcR stimulation had distinct effects on p63 protein expression, particularly leading to induction in subset #8, accompanied by increased CLL cell survival. This pro-survival effect was also supported by siRNA-mediated downregulation of p63 expression resulting in increased apoptosis. In conclusion, we report that DNA methylation profiles may vary even among CLL patients with similar somatic hypermutation status, supporting a compartmentalized approach to dissecting CLL biology. Furthermore, we highlight p63 as a novel prosurvival factor in CLL, thus identifying another piece of the complex puzzle of clinical aggressiveness. What's new? In chronic lymphocytic leukemia (CLL), cases with unmutated immunoglobulin receptors (U-CLL) are generally associated with inferior outcome, albeit still displaying considerable heterogeneity. Might such diff, De 3 första författarna delar förstaförfattarskapet.

Published
2019
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3. Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Author

Baliakas, Panagiotis, Moysiadis, Theodoros, Hadzidimitriou, Anastasia, Xochelli, Aliki, Jeromin, Sabine, Agathangelidis, Andreas, Mattsson, Mattias, Sutton, Lesley Ann, Minga, Eva, Scarfo, Lydia, Rossi, Davide, Davis, Zadie, Villamor, Neus, Parker, Helen, Kotaskova, Jana, Stalika, Evangelia, Plevova, Karla, Mansouri, Larry, Cortese, Diego, Navarro, Alba, Delgado, Julio, Larrayoz, Marta, Young, Emma, Anagnostopoulos, Achilles, Smedby, Karin E., Juliusson, Gunnar, Sheehy, Oonagh, Catherwood, Mark, Strefford, Jonathan C., Stavroyianni, Niki, Belessi, Chrysoula, Pospisilova, Sarka, Oscier, David, Gaidano, Gianluca, Campo, Elias, Haferlach, Claudia, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Moysiadis, Theodoros, Hadzidimitriou, Anastasia, Xochelli, Aliki, Jeromin, Sabine, Agathangelidis, Andreas, Mattsson, Mattias, Sutton, Lesley Ann, Minga, Eva, Scarfo, Lydia, Rossi, Davide, Davis, Zadie, Villamor, Neus, Parker, Helen, Kotaskova, Jana, Stalika, Evangelia, Plevova, Karla, Mansouri, Larry, Cortese, Diego, Navarro, Alba, Delgado, Julio, Larrayoz, Marta, Young, Emma, Anagnostopoulos, Achilles, Smedby, Karin E., Juliusson, Gunnar, Sheehy, Oonagh, Catherwood, Mark, Strefford, Jonathan C., Stavroyianni, Niki, Belessi, Chrysoula, Pospisilova, Sarka, Oscier, David, Gaidano, Gianluca, Campo, Elias, Haferlach, Claudia, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Abstract

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.

Published
2019
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4. 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
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5. Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia : From Patient Material To Sequence Interpretation

Author

Agathangelidis, Andreas, Sutton, Lesley Ann, Hadzidimitriou, Anastasia, Tresoldi, Cristina, Langerak, Anton W., Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Stamatopoulos, Kostas, Ghia, Paolo, Agathangelidis, Andreas, Sutton, Lesley Ann, Hadzidimitriou, Anastasia, Tresoldi, Cristina, Langerak, Anton W., Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Stamatopoulos, Kostas, and Ghia, Paolo

Abstract

During B cell maturation, the complex process of immunoglobulin (IG) gene V(D)J recombination coupled with somatic hypermutation (SHM) gives rise to a unique DNA sequence within each individual B cell. Since B cell malignancies result from the clonal expansion of a single cell, IG genes represent a unique molecular signature common to all the malignant cells within an individual patient; thus, IG gene rearrangements can be used as clonal markers. In addition to serving as an important clonal identifier, the IG gene sequence can act as a 'molecular timeline' since it is associated with specific developmental stages and hence reflects the history of the B cell involved in the neoplastic transformation. Moreover, for certain malignancies, in particular chronic lymphocytic leukemia (CLL), the IG gene sequence holds prognostic and potentially predictive capabilities. That said, extrapolating meaningful conclusions from IG gene sequence analysis would be impossible if robust methods and tools were not available to aid in their analysis. This article, drawing on the vast experience of the European Research Initiative on CLL (ERIC), details the technical aspects and essential requirements necessary to ensure reliable and reproducible IG gene sequence analysis in CLL, a test that is now recommended for all CLL patients prior to treatment. More specifically, the various analytical stages are described ranging from the identification of the clonotypic IG gene rearrangement and the determination of the nucleotide sequence to the accurate clinical interpretation of the IG gene sequence data., De två första författarna delar förstaförfattarskapet.

Published
2018
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6. Numerous Ontogenetic Roads to Mantle Cell Lymphoma : Immunogenetic and Immunohistochemical Evidence

Author

Pouliou, Evi, Xochelli, Aliki, Kanellis, George, Stalika, Evangelia, Sutton, Lesley-Ann, Navarro, Alba, Agathangelidis, Andreas, Dimosthenous, Kypros, Anagnostopoulos, Achilles, Patsouris, Efstratios, Korkolopoulou, Penelope, Sundström, Christer, Ghia, Paolo, Ponzoni, Maurilio, Sander, Birgitta, Campo, Elias, Rosenquist, Richard, Hadzidimitriou, Anastasia, Stamatopoulos, Kostas, Papadaki, Theodora, Pouliou, Evi, Xochelli, Aliki, Kanellis, George, Stalika, Evangelia, Sutton, Lesley-Ann, Navarro, Alba, Agathangelidis, Andreas, Dimosthenous, Kypros, Anagnostopoulos, Achilles, Patsouris, Efstratios, Korkolopoulou, Penelope, Sundström, Christer, Ghia, Paolo, Ponzoni, Maurilio, Sander, Birgitta, Campo, Elias, Rosenquist, Richard, Hadzidimitriou, Anastasia, Stamatopoulos, Kostas, and Papadaki, Theodora

Abstract

To obtain insight into the ontogeny of mantle cell lymphoma (MCL), we assessed 206 patients from a morphological, immunohistochemical, and immunogenetic perspective. Our series included nodal (n = 151), extranodal. (n = 28), and primary splenic (n = 27) MCL cases. Skewing of the immunoglobulin heavy variable (IGHV) gene repertoire was noted, with only four IGHV genes accounting for 46% of cases and approximately 70% of cases (107/154) bearing an imprint of somatic hypermutation (SHM) ranging from minimalto pronounced. Interestingly, a distinctive immunophenotypic and immunogenetic profile was identified for primary splenic MCL, which was enriched for DBA.44-positive cases (P < 0.001) and used the IGHV1-8 gene more frequently (P = 0.02) compared to nodal or extranodal cases, alluding to distinct immunopathogenetic and antigen selection processes. Expression of CD27 (considered a marker of activated B cells) was generally dissociated from SHM and was more prevalent in cases with no or minimal/borderline SHM. These findings support the idea that antigen drive is relevant for most MCL cases, although the specific antigens and the precise location of affinity maturation remain to be elucidated. Moreover, they raise the intriguing hypothesis of multiple cellular origins for MCL.

Published
2017
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7. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia : updated ERIC recommendations

Author

Rosenquist, Richard, Ghia, P., Hadzidimitriou, A., Sutton, Lesley Ann, Agathangelidis, A., Baliakas, Panagiotis, Darzentas, N., Giudicelli, V., Lefranc, M-P, Langerak, A. W., Belessi, C., Davi, F., Stamatopoulos, Kostas, Rosenquist, Richard, Ghia, P., Hadzidimitriou, A., Sutton, Lesley Ann, Agathangelidis, A., Baliakas, Panagiotis, Darzentas, N., Giudicelli, V., Lefranc, M-P, Langerak, A. W., Belessi, C., Davi, F., and Stamatopoulos, Kostas

Published
2017
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8. 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
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9. Immunoglobulin genes in chronic lymphocytic leukemia : key to understanding the disease and improving risk stratification

Author

Sutton, Lesley Ann, Hadzidimitriou, Anastasia, Baliakas, Panagiotis, Agathangelidis, Andreas, Langerak, Anton W., Stilgenbauer, Stephan, Pospisilova, Sarka, Davis, Zadie, Forconi, Francesco, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, Sutton, Lesley Ann, Hadzidimitriou, Anastasia, Baliakas, Panagiotis, Agathangelidis, Andreas, Langerak, Anton W., Stilgenbauer, Stephan, Pospisilova, Sarka, Davis, Zadie, Forconi, Francesco, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2017
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10. Tp53 gene p72R polymorphism in chronic lymphocytic leukemia : incidence and clinical significance amongst cases with unmutated immunoglobulin receptors

Author

Gemenetzi, Katerina, Galigalidou, Chrysi, Vlachonikola, Elisavet, Stalika, Evangelia, Xochelli, Aliki, Baliakas, Panagiotis, Karypidou, Maria, Touloumenidou, Tasoula, Minga, Evangelia, Douka, Vasiliki, Iskas, Michalis, Athanasiadou, Anastasia, Makris, Antonios, Stavroyianni, Niki, Anagnostopoulos, Achilles, Hadzidimitriou, Anastasia, Stamatopoulos, Kostas, Gemenetzi, Katerina, Galigalidou, Chrysi, Vlachonikola, Elisavet, Stalika, Evangelia, Xochelli, Aliki, Baliakas, Panagiotis, Karypidou, Maria, Touloumenidou, Tasoula, Minga, Evangelia, Douka, Vasiliki, Iskas, Michalis, Athanasiadou, Anastasia, Makris, Antonios, Stavroyianni, Niki, Anagnostopoulos, Achilles, Hadzidimitriou, Anastasia, and Stamatopoulos, Kostas

Published
2017
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11. Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors

Author

Mastrodemou, Semeli, Stalika, Evangelia, Vardi, Anna, Gemenetzi, Katerina, Spanoudakis, Michalis, Karypidou, Maria, Mavroudi, Irene, Hadzidimitriou, Anastasia, Stavropoulos-Giokas, Catherine, Papadaki, Helen A., Stamatopoulos, Kostas, Mastrodemou, Semeli, Stalika, Evangelia, Vardi, Anna, Gemenetzi, Katerina, Spanoudakis, Michalis, Karypidou, Maria, Mavroudi, Irene, Hadzidimitriou, Anastasia, Stavropoulos-Giokas, Catherine, Papadaki, Helen A., and Stamatopoulos, Kostas

Abstract

Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8(+) cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV-TRBD-TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.

Published
2017
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12. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

Author

Sutton, Lesley-Ann, Young, Emma, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Moysiadis, Theodoros, Plevova, Karla, Rossi, Davide, Kminkova, Jana, Stalika, Evangelia, Pedersen, Lone Bredo, Malcikova, Jitka, Agathangelidis, Andreas, Davis, Zadie, Mansouri, Larry, Scarfo, Lydia, Boudjoghra, Myriam, Navarro, Alba, Muggen, Alice F., Yan, Xiao-Jie, Nguyen-Khac, Florence, Larrayoz, Marta, Panagiotidis, Panagiotis, Chiorazzi, Nicholas, Niemann, Carsten Utoft, Belessi, Chrysoula, Campo, Elias, Strefford, Jonathan C., Langerak, Anton W., Oscier, David, Gaidano, Gianluca, Pospisilova, Sarka, Davi, Frederic, Ghia, Paolo, Stamatopoulos, Kostas, Rosenquist, Richard, Sutton, Lesley-Ann, Young, Emma, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Moysiadis, Theodoros, Plevova, Karla, Rossi, Davide, Kminkova, Jana, Stalika, Evangelia, Pedersen, Lone Bredo, Malcikova, Jitka, Agathangelidis, Andreas, Davis, Zadie, Mansouri, Larry, Scarfo, Lydia, Boudjoghra, Myriam, Navarro, Alba, Muggen, Alice F., Yan, Xiao-Jie, Nguyen-Khac, Florence, Larrayoz, Marta, Panagiotidis, Panagiotis, Chiorazzi, Nicholas, Niemann, Carsten Utoft, Belessi, Chrysoula, Campo, Elias, Strefford, Jonathan C., Langerak, Anton W., Oscier, David, Gaidano, Gianluca, Pospisilova, Sarka, Davi, Frederic, Ghia, Paolo, Stamatopoulos, Kostas, and Rosenquist, Richard

Abstract

We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22-34%), often in association with trisomy 12, and was significantly different (P<0.001) to the frequency observed in subset #2 (4%, aggressive disease, variable somatic hypermutation status) and subset #4 (1%, indolent disease, mutated immunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets# 2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s).

Published
2016
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13. Molecular Evidence for Antigen Drive in the Natural History of Mantle Cell Lymphoma

Author

Xochelli, Aliki, Sutton, Lesley-Ann, Agathangelidis, Andreas, Stalika, Evangelia, Karypidou, Maria, Marantidou, Fotini, Navarro Lopez, Alba, Papadopoulos, Giorgos, Supikova, Jana, Groenen, Patricia, Boudjogra, Myriam, Sundström, Christer, Ponzoni, Maudilio, Francova, Hana Skuhrova, Anagnostopoulos, Achilles, Pospisilova, Sarka, Papadaki, Theodora, Tzovaras, Dimitris, Ghia, Paolo, Pott, Christiane, Davi, Frederic, Campo, Elias, Rosenquist, Richard Brandell, Hadzidimitriou, Anastasia, Belessi, Chrysoula, Stamatopoulos, Kostas, Xochelli, Aliki, Sutton, Lesley-Ann, Agathangelidis, Andreas, Stalika, Evangelia, Karypidou, Maria, Marantidou, Fotini, Navarro Lopez, Alba, Papadopoulos, Giorgos, Supikova, Jana, Groenen, Patricia, Boudjogra, Myriam, Sundström, Christer, Ponzoni, Maudilio, Francova, Hana Skuhrova, Anagnostopoulos, Achilles, Pospisilova, Sarka, Papadaki, Theodora, Tzovaras, Dimitris, Ghia, Paolo, Pott, Christiane, Davi, Frederic, Campo, Elias, Rosenquist, Richard Brandell, Hadzidimitriou, Anastasia, Belessi, Chrysoula, and Stamatopoulos, Kostas

Abstract

To further our understanding about antigen involvement in mantle cell Lymphoma (MCL), we analyzed the expression levels of activation-induced cytidine deaminase (AID), a key player in B-cell responses to antigen triggering, in 133 MCL cases; assessed the functionality of AID by evaluating in vivo class switch recombination in 52 MCL cases; and sought for indications of ongoing antigen interactions by exploring intraclonal diversification within 14 MCL cases. The AID full-length transcript and the most frequent splice variants (AID-Delta E4a, AID-Delta E) were detected in 128 (96.2%), 96 (72.2%), and 130 cases (97.7%), respectively. Higher AID full-Length transcript levels were significantly associated (P < 0.001) with Lack of somatic hypermutation within the clonotypic immunoglobulin heavy variable (IGHV) genes. Median AID transcript levels were higher in lymph node material compared to cases in which peripheral blood was analyzed, implying that clonal behavior is influenced by the microenvironment. Switched tumor-derived IGHV-IGHD-IGHJ transcripts were identified in 5 of 52 cases (9.6%), all of which displayed somatic hypermutation and AID-mRNA expression. Finally, although most cases exhibited low levels of intraclonal diversification, analysis of the mutational activity revealed a precise targeting of somatic hypermutation indicative of an active, ongoing interaction with antigen(s). Collectively, these findings strongly allude to antigen involvement in the natural history of MCL, further challenging the notion of antigen naivety.

Published
2015
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14. Immunoglobulin heavy variable (IGHV) genes and alleles : new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia

Author

Xochelli, Aliki, Agathangelidis, Andreas, Kavakiotis, Ioannis, Minga, Evangelia, Sutton, Lesley Ann, Baliakas, Panagiotis, Chouvarda, Ioanna, Giudicelli, Veronique, Vlahavas, Ioannis, Maglaveras, Nikos, Bonello, Lisa, Trentin, Livio, Tedeschi, Alessandra, Panagiotidis, Panagiotis, Geisler, Christian, Langerak, Anton W., Pospisilova, Sarka, Jelinek, Diane F., Oscier, David, Chiorazzi, Nicholas, Darzentas, Nikos, Davi, Fred, Ghia, Paolo, Rosenquist, Richard, Hadzidimitriou, Anastasia, Belessi, Chrysoula, Lefranc, Marie-Paule, Stamatopoulos, Kostas, Xochelli, Aliki, Agathangelidis, Andreas, Kavakiotis, Ioannis, Minga, Evangelia, Sutton, Lesley Ann, Baliakas, Panagiotis, Chouvarda, Ioanna, Giudicelli, Veronique, Vlahavas, Ioannis, Maglaveras, Nikos, Bonello, Lisa, Trentin, Livio, Tedeschi, Alessandra, Panagiotidis, Panagiotis, Geisler, Christian, Langerak, Anton W., Pospisilova, Sarka, Jelinek, Diane F., Oscier, David, Chiorazzi, Nicholas, Darzentas, Nikos, Davi, Fred, Ghia, Paolo, Rosenquist, Richard, Hadzidimitriou, Anastasia, Belessi, Chrysoula, Lefranc, Marie-Paule, and Stamatopoulos, Kostas

Abstract

Ieext generation sequencing studies in Homo sapiens have identified novel immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in the international ImMunoGeneTics information system (IMGT) GENE-DB and reference directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly associated with patient outcome. Correct determination of this parameter strictly depends on the comparison of the nucleotide sequence of the clonotypic rearranged IGHV gene with that of the closest germline counterpart. Consequently, changes in the reference directories could, in principle, affect the correct interpretation of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG heavy chain (IGH) rearrangement sequences from our consortium both before and after the latest update of the IMGT/V-QUEST reference directory. Differences were identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %), changes concerned only the IGHV gene or allele name, whereas a change in the percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in 50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational set. In conclusion, recent changes in the IMGT reference directories affected the interpretation of SHM in a sizeable number of IGH rearrangement sequences from CLL patients. This indicates that both physicians and researchers should consider a re-evaluation of IG sequence data, especially for those IGH rearrangement sequences that, up to date, have a GI close to 98 %, where caution is warranted.

Published
2015
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15. Recurrent mutations refine prognosis in chronic lymphocytic leukemia

Author

Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, Rosenquist, Richard, Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, and Rosenquist, Richard

Abstract

Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods., De tre sista författarna delar sistaförfattarskapet.

Published
2015
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16. 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, 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, Moreno, Denis, 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, Ghia, Paolo, Rosenquist, Richard Brandell, Stamatopoulos, Kostas, Baliakas, Panagiotis, Agathangelidis, Andreas, Hadzidimitriou, Anastasia, Sutton, Lesley-Ann, Minga, Eva, 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, Moreno, Denis, 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, Ghia, Paolo, Rosenquist, Richard Brandell, 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
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17. REFINING PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH SOMATICALLY HYPERMUTATED B-CELL RECEPTORS : A NOVEL PROGNOSTIC INDEX ON BEHALF OF THE EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC)

Author

Baliakas, Panagiotis, Hadzidimitriou, A., Mattsson, Mattias, Xochelli, Aliki, Sutton, L. A., Minga, E., Scarfo, L., Rossi, D., Davis, Z., Agathangelidis, A., Villamor, N., Parker, H., Kotaskova, J., Stalika, E., Plevova, K., Mansouri, Larry, Cortese, Diego, Navarro Lopez, A., Delgado, J., Larrayoz, M., Anagnostopoulos, A., Belessi, C., Smedby, K. E., Juliusson, G., Strefford, J. C., Pospisilova, S., Oscier, D., Gaidano, G., Campo, E., Ghia, P., Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Hadzidimitriou, A., Mattsson, Mattias, Xochelli, Aliki, Sutton, L. A., Minga, E., Scarfo, L., Rossi, D., Davis, Z., Agathangelidis, A., Villamor, N., Parker, H., Kotaskova, J., Stalika, E., Plevova, K., Mansouri, Larry, Cortese, Diego, Navarro Lopez, A., Delgado, J., Larrayoz, M., Anagnostopoulos, A., Belessi, C., Smedby, K. E., Juliusson, G., Strefford, J. C., Pospisilova, S., Oscier, D., Gaidano, G., Campo, E., Ghia, P., Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2015

18. Prognostic relevance of MYD88 mutations in CLL : the jury is still out

Author

Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Agathangelidis, Andreas, Rossi, Davide, Sutton, Lesley-Ann, Kminkova, Jana, Scarfo, Lydia, Pospisilova, Sarka, Gaidano, Gianluca, Stamatopoulos, Kostas, Ghia, Paolo, Rosenquist, Richard, Baliakas, Panagiotis, Hadzidimitriou, Anastasia, Agathangelidis, Andreas, Rossi, Davide, Sutton, Lesley-Ann, Kminkova, Jana, Scarfo, Lydia, Pospisilova, Sarka, Gaidano, Gianluca, Stamatopoulos, Kostas, Ghia, Paolo, and Rosenquist, Richard

Published
2015
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19. An entity evolving into a community: defining the common ancestor and evolutionary trajectory of chronic lymphocytic leukemia stereotyped subset #4

Author

Sutton, Lesley-Ann, Papadopoulos, Giorgos, Hadzidimitriou, Anastasia, Papadopoulos, Stavros, Kostareli, Efterpi, Rosenquist, Richard, Tzovaras, Dimitrios, Stamatopoulos, Kostas, Sutton, Lesley-Ann, Papadopoulos, Giorgos, Hadzidimitriou, Anastasia, Papadopoulos, Stavros, Kostareli, Efterpi, Rosenquist, Richard, Tzovaras, Dimitrios, and Stamatopoulos, Kostas

Abstract

Patients with chronic lymphocytic leukemia (CLL) assigned to stereotyped subset #4 express highly homologous B-cell receptor immunoglobulin (BcR IG) sequences with intense intraclonal diversification (ID) in the context of ongoing somatic hypermutation (SHM). Their remarkable biological and clinical similarities strongly support derivation from a common ancestor. We here revisited ID in subset #4 CLL in order to reconstruct their evolutionary history as a community of related clones. To this end, using specialized bioinformatics tools we assessed both IGHV-IGHD-IGHJ rearrangements (n=511) and IGKV-IGKJ rearrangements (n=397) derived from 8 subset #4 cases. Due to high sequence relatedness, a number of subclonal clusters from different cases lay very close to one another, forming a core from which clusters exhibiting greater variation stemmed. Minor subclones from individual cases were mutated to such an extent that they now resembled the sequences of another patient. Viewing the entire subset #4 dataset as a single entity branching through diversification, enabled inference of a common sequence representing the putative ancestral BcR IG expressed by their still elusive common progenitor. These results have implications for improved understanding of the ontogeny of CLL subset #4, as well as the design of studies concerning the antigenic specificity of the clonotypic BcR IGs., De två första författarna delar förstaförfattarskapet.

Published
2014
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20. Immunoglobulin Heavy Variable Genes and Alleles : New Entities, New Names and Implications for Research and Prognostication in CLL

Author

Xochelli, A., Agathangelidis, A., Kavakiotis, I., Minga, E., Sutton, L. A., Baliakas, Panagiotis, Chouvarda, I., Giudicelli, V., Vlahavas, I., Maglaveras, N., Bonello, L., Trentin, L., Montillo, M., Panagiotidis, P., Geisler, C., Langerak, A. W., Pospisilova, S., Jelinek, D. F., Oscier, D., Chiorazzi, N., Darzentas, N., Davi, F., Ghia, P., Rosenquist, Richard Brandell, Hadzidimitriou, A., Belessi, C., Lefranc, M. P., Stamatopoulos, K., Xochelli, A., Agathangelidis, A., Kavakiotis, I., Minga, E., Sutton, L. A., Baliakas, Panagiotis, Chouvarda, I., Giudicelli, V., Vlahavas, I., Maglaveras, N., Bonello, L., Trentin, L., Montillo, M., Panagiotidis, P., Geisler, C., Langerak, A. W., Pospisilova, S., Jelinek, D. F., Oscier, D., Chiorazzi, N., Darzentas, N., Davi, F., Ghia, P., Rosenquist, Richard Brandell, Hadzidimitriou, A., Belessi, C., Lefranc, M. P., and Stamatopoulos, K.

Published
2014

21. Not All IGHV3-21 CLL Are Equal : Subset #2 Displays a Distinctive Clinicobiological Profile with Remarkable Similarities to Subset #169, its Close Immunogenetic Relative

Author

Baliakas, Panagiotis, Hadzidimitriou, A., Sutton, L. A., Minga, E., Agathangelidis, A., Tsanousa, A., Scarfo, L., Davis, Z., Yan, X. J., Shanafelt, T., Plevova, K., Sandberg, Y., Vojdeman, F. J., Boudjogra, M., Tzenou, T., Chatzouli, M., Chu, C. C., Veronese, S., Gardiner, A., Mansouri, Larry, Smedby, K. E., Pedersen, L. B., Moreno, D., Van Lom, K., Giudicelli, V., Francova, H. S., Nguyen-Khac, F., Panagiotidis, P., Juliusson, G., Angelis, L., Anagnostopoulos, A., Lefranc, M. P., Trentin, L., Catherwood, M., Montillo, M., Geisler, C., Langerak, A. W., Pospisilova, S., Chiorazzi, N., Oscier, D., Jelinek, D., Darzentas, N., Belessi, C., Davi, F., Ghia, P., Rosenquist, Richard Brandell, Stamatopoulos, K., Baliakas, Panagiotis, Hadzidimitriou, A., Sutton, L. A., Minga, E., Agathangelidis, A., Tsanousa, A., Scarfo, L., Davis, Z., Yan, X. J., Shanafelt, T., Plevova, K., Sandberg, Y., Vojdeman, F. J., Boudjogra, M., Tzenou, T., Chatzouli, M., Chu, C. C., Veronese, S., Gardiner, A., Mansouri, Larry, Smedby, K. E., Pedersen, L. B., Moreno, D., Van Lom, K., Giudicelli, V., Francova, H. S., Nguyen-Khac, F., Panagiotidis, P., Juliusson, G., Angelis, L., Anagnostopoulos, A., Lefranc, M. P., Trentin, L., Catherwood, M., Montillo, M., Geisler, C., Langerak, A. W., Pospisilova, S., Chiorazzi, N., Oscier, D., Jelinek, D., Darzentas, N., Belessi, C., Davi, F., Ghia, P., Rosenquist, Richard Brandell, and Stamatopoulos, K.

Published
2014

23. Matched Pattern Discovery Across Paired Immunoglobulin Heavy and Light Chains in CLL Reveals Unique Subset-Defining Amino Acid Associations

Author

Sutton, L. A., Moschonas, P., Vardi, A., Bikos, V., Yan, X. J., Chatzouli, M., Anagnostopoulos, A., Belessi, C., Chiorazzi, N., Rosenquist, Richard Brandell, Tzovaras, D., Stamatopoulos, Kostas, Hadzidimitriou, A., Sutton, L. A., Moschonas, P., Vardi, A., Bikos, V., Yan, X. J., Chatzouli, M., Anagnostopoulos, A., Belessi, C., Chiorazzi, N., Rosenquist, Richard Brandell, Tzovaras, D., Stamatopoulos, Kostas, and Hadzidimitriou, A.

Published
2014

24. Skewing of the T-Cell Receptor Repertoire in Chronic Lymphocytic Leukemia : What Lies Beneath?

Author

Vardi, A., Agathangelidis, A., Stalika, E., Sutton, L. A., Karypidou, M., Anagnostopoulos, A., Hadzidimitriou, A., Ghia, P., Rosenquist, Richard Brandell, Stamatopoulos, K., Vardi, A., Agathangelidis, A., Stalika, E., Sutton, L. A., Karypidou, M., Anagnostopoulos, A., Hadzidimitriou, A., Ghia, P., Rosenquist, Richard Brandell, and Stamatopoulos, K.

Published
2014

25. 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
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