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1. How to manage patients with germline DDX41 variants: Recommendations from the Nordic working group on germline predisposition for myeloid neoplasms

Author

Panagiotis Baliakas, Bianca Tesi, Jörg Cammenga, Asbjørg Stray‐Pedersen, Kirsi Jahnukainen, Mette Klarskov Andersen, Helena Ågerstam, Maria Creignou, Ingunn Dybedal, Klas Raaschou‐Jensen, Kirsten Grønbæk, Outi Kilpivaara, Eva Hellström Lindberg, and Ulla Wartiovaara‐Kautto

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Increasing recognition of germline DDX41 variants in patients with hematological malignancies prompted us to provide DDX41‐specific recommendations for diagnosis, surveillance, and treatment. Causative germline variants in the DDX41 predispose to the development of myeloid neoplasms (MNs), especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Almost 3%–5% of all patients with MDS or AML carry a pathogenic or likely pathogenic germline DDX41 variant, while half of them acquire a somatic second hit in the other allele. DDX41‐associated MNs exhibit unique clinical characteristics compared to other hematological malignancies with germline predisposition: MNs occur mostly at advanced age and follow an indolent clinical course. Male carriers are more prone to develop MDS or AML than females. DDX41‐associated MN is often hypoplastic, and the malignancy may be preceded by cytopenias.

Published
2024
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2. P513: MOLECULAR PATTERN BY AGE AND OVERALL SURVIVAL IN ACUTE MYELOID LEUKEMIA: A POPULATION-BASED STUDY FROM THE SWEDISH AML REGISTRY.

Author

Gunnar Juliusson, Christer Nilsson, Sören Lehmann, Martin Jädersten, Lovisa Wennström, Linda Fogelstrand, Panagiotis Baliakas, Tatjana Pandzic, Lucia Cavelier, Anna Eriksson, Albin Österroos, Anna Thunström, Benedicte Piauger, Bertil Uggla, Emma Ölander, Gustav Orrsjö, Jörg Cammenga, Kristina Myhr-Eriksson, Petter Willner Hjelm, Stefan Deneberg, Thoas Fioretos, Martin Höglund, and Vladimir Lazarevic

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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3. P506: CLINICAL VALIDATION OF THE NORDIC GUIDELINES FOR GERMLINE TESTING IN MYELOID NEOPLASMS: RESULTS FROM A MULTI-CENTER PROSPECTIVE COHORT STUDY

Author

Bianca Tesi, Anna Eriksson, Berivan Baskin, Vladimir Lazarevic, Stefan Deneberg, Martin Höglund, Linda Fogelstrand, Johanna Ungerstedt, Tatjana Pandzic, Magnus Tobiasson, Hege Gravdahl Garelius, Ekaterina Kuchinskaya, Fredrik Persson, Helena Ågerstam, Bertil Uggla, Helene Hallböök, Thoas Fioretos, Ann-Charlotte Thuresson, Sören Lehmann, Claes Ladenvall, Gisela Barbany, Lovisa Vennström, Elisabeth Ejerblad, Lucia Cavelier, Jörg Cammenga, Martin Jädersten, Eva Hellström Lindberg, and Panagiotis Baliakas

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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4. T cell receptor gene repertoire profiles in subgroups of patients with chronic lymphocytic leukemia bearing distinct genomic aberrations

Author

Elisavet Vlachonikola, Nikolaos Pechlivanis, Georgios Karakatsoulis, Electra Sofou, Glykeria Gkoliou, Sabine Jeromin, Niki Stavroyianni, Pamela Ranghetti, Lydia Scarfo, Cecilia Österholm, Larry Mansouri, Sofia Notopoulou, Alexandra Siorenta, Achilles Anagnostopoulos, Paolo Ghia, Claudia Haferlach, Richard Rosenquist, Fotis Psomopoulos, Anastasia Kouvatsi, Panagiotis Baliakas, Kostas Stamatopoulos, and Anastasia Chatzidimitriou

Subjects
T cell receptor (TR) gene repertoire, chronic lymphocytic leukemia (CLL), recurrent genomic aberrations, neoepitopes, T cell based immunotherapies, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundMicroenvironmental interactions of the malignant clone with T cells are critical throughout the natural history of chronic lymphocytic leukemia (CLL). Indeed, clonal expansions of T cells and shared clonotypes exist between different CLL patients, strongly implying clonal selection by antigens. Moreover, immunogenic neoepitopes have been isolated from the clonotypic B cell receptor immunoglobulin sequences, offering a rationale for immunotherapeutic approaches. Here, we interrogated the T cell receptor (TR) gene repertoire of CLL patients with different genomic aberration profiles aiming to identify unique signatures that would point towards an additional source of immunogenic neoepitopes for T cells.Experimental designTR gene repertoire profiling using next generation sequencing in groups of patients with CLL carrying one of the following copy-number aberrations (CNAs): del(11q), del(17p), del(13q), trisomy 12, or gene mutations in TP53 or NOTCH1.ResultsOligoclonal expansions were found in all patients with distinct recurrent genomic aberrations; these were more pronounced in cases bearing CNAs, particularly trisomy 12, rather than gene mutations. Shared clonotypes were found both within and across groups, which appeared to be CLL-biased based on extensive comparisons against TR databases from various entities. Moreover, in silico analysis identified TR clonotypes with high binding affinity to neoepitopes predicted to arise from TP53 and NOTCH1 mutations.ConclusionsDistinct TR repertoire profiles were identified in groups of patients with CLL bearing different genomic aberrations, alluding to distinct selection processes. Abnormal protein expression and gene dosage effects associated with recurrent genomic aberrations likely represent a relevant source of CLL-specific selecting antigens.

Published
2023
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6. Five Percent Variant Allele Frequency Is a Reliable Reporting Threshold for TP53 Variants Detected by Next Generation Sequencing in Chronic Lymphocytic Leukemia in the Clinical Setting

Author

Tatjana Pandzic, Claes Ladenvall, Marie Engvall, Mattias Mattsson, Monica Hermanson, Lucia Cavelier, Viktor Ljungström, and Panagiotis Baliakas

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The clinical significance of small TP53 clones detected with next generation sequencing (NGS) in chronic lymphocytic leukemia is an issue of active debate. According to the official guidelines, treatment decisions should be guided only by variants with variant allele frequency (VAF) ≥10%. We present data on 325 consecutive patients with chronic lymphocytic leukemia analyzed with NGS. In total 47 pathogenic/likely pathogenic (P/LP), TP53 variants were detected in 26 patients (8%). Eleven of these (23%) were in the 5% to 10% VAF range and reported according to our institutional policy. All TP53 variants in the 5% to 10% VAF range were confirmed (100% concordance) with a second NGS panel. Our results where further validated with the performance of Sanger sequencing and digital droplet PCR (ddPCR). In 12 patients with available fluorescence in situ hybridization data and TP53 mutations within 5% to 10% VAF, deletion of chromosome 17p (del(17p)) was detectable in only 1 patient. We propose a robust diagnostic algorithm, which allows the safe detection and reporting of TP53 variants with VAF down to 5% in the clinical setting. Our study provides evidence that NGS is equally potent to detect variants with VAF 5% to 10% compared to those with VAF 10% to 15%, highlighting the urgent need for harmonization of NGS methodologies across diagnostic laboratories.

Published
2022
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7. Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

Author

Panagiotis Baliakas, Blanca Espinet, Clemens Mellink, Marie Jarosova, Anastasia Athanasiadou, Paolo Ghia, Arnon P. Kater, David Oscier, Claudia Haferlach, Kostas Stamatopoulos, and on behalf of ERIC, the European Research Initiative on CLL

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Mounting evidence underscores the clinical value of cytogenetic analysis in chronic lymphocytic leukemia (CLL), particularly as it allows the identification of complex karyotype, that has recently emerged as a prognostic and potentially predictive biomarker. That said, explicit recommendations regarding the methodology and clinical interpretation of either chromosome banding analysis (CBA) or chromosome microarray analysis (CMA) are still lacking. We herein present the consensus of the Cytogenetic Steering Scientific Committee of ERIC, the European Research Initiative on CLL, regarding methodological issues as well as clinical interpretation of CBA/CMA and discuss their relevance in CLL. ERIC considers CBA standardized and feasible for CLL on the condition that standards are met, extending from the use of novel mitogens to the accurate interpretation of the findings. On the other hand, CMA, is also standardized, however, robust data on its clinical utility are still scarce. In conclusion, cytogenetic analysis is not yet mature enough to guide treatment choices in CLL. That notwithstanding, ERIC encourages the wide application of CBA, and potentially also CMA, in clinical trials in order to obtain robust evidence regarding the predictive value of specific cytogenetic profiles towards refining risk stratification and improving the management of patients with CLL.

Published
2022
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8. Landscape of TP53 Alterations in Chronic Lymphocytic Leukemia via Data Mining Mutation Databases

Author

Thierry Soussi and Panagiotis Baliakas

Subjects
mutation database, TP53 mutation, chronic lymphocytic leukemia, variant classification guidelines, genetic analysis model, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Locus-specific databases are invaluable tools for both basic and clinical research. The extensive information they contain is gathered from the literature and manually curated by experts. Cancer genome sequencing projects generate an immense amount of data, which are stored directly in large repositories (cancer genome databases). The presence of a TP53 defect (17p deletion and/or TP53 mutations) is an independent prognostic factor in chronic lymphocytic leukemia (CLL) and TP53 status analysis has been adopted in routine clinical practice. For that reason, TP53 mutation databases have become essential for the validation of the plethora of TP53 variants detected in tumor samples. TP53 profiles in CLL are characterized by a great number of subclonal TP53 mutations with low variant allelic frequencies and the presence of multiple minor subclones harboring different TP53 mutations. In this review, we describe the various characteristics of the multiple levels of heterogeneity of TP53 variants in CLL through the analysis of TP53 mutation databases and the utility of their diagnosis in the clinic.

Published
2022
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9. Biology and Treatment of High-Risk CLL: Significance of Complex Karyotype

Author

Thomas Chatzikonstantinou, Christos Demosthenous, and Panagiotis Baliakas

Subjects
CLL (chronic lymphocytic leukemia), prognosis, prediction, high-risk, complex karyotype (CK), cytogenetic complexity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Several reports highlight the clinical significance of cytogenetic complexity, namely, complex karyotype (CK) identified though the performance of chromosome banding analysis (CBA) in chronic lymphocytic leukemia. Indeed, apart from a number of studies underscoring the prognostic and predictive value of CK in the chemo(immune)therapy era, mounting evidence suggests that CK could serve as an independent prognosticator and predictor even in patients treated with novel agents. In the present review, we provide an overview of the current knowledge regarding the clinical impact of CK in CLL, touching upon open issues related to the incorporation of CK in the clinical setting.

Published
2021
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10. ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants

Author

Xi Luo, Simone Feurstein, Shruthi Mohan, Christopher C. Porter, Sarah A. Jackson, Sioban Keel, Michael Chicka, Anna L. Brown, Chimene Kesserwan, Anupriya Agarwal, Minjie Luo, Zejuan Li, Justyne E. Ross, Panagiotis Baliakas, Daniel Pineda-Alvarez, Courtney D. DiNardo, Alison A. Bertuch, Nikita Mehta, Tom Vulliamy, Ying Wang, Kim E. Nichols, Luca Malcovati, Michael F. Walsh, Lesley H. Rawlings, Shannon K. McWeeney, Jean Soulier, Anna Raimbault, Mark J. Routbort, Liying Zhang, Gabriella Ryan, Nancy A. Speck, Sharon E. Plon, David Wu, and Lucy A. Godley

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Standardized variant curation is essential for clinical care recommendations for patients with inherited disorders. Clinical Genome Resource (ClinGen) variant curation expert panels are developing disease-associated gene specifications using the 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines to reduce curation discrepancies. The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) was created collaboratively between the American Society of Hematology and ClinGen to perform gene- and disease-specific modifications for inherited myeloid malignancies. The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies. The 28 ACMG/AMP codes were tailored for RUNX1 variants by modifying gene/disease specifications, incorporating strength adjustments of existing rules, or both. Key specifications included calculation of minor allele frequency thresholds, formulating a semi-quantitative approach to counting multiple independent variant occurrences, identifying functional domains and mutational hotspots, establishing functional assay thresholds, and characterizing phenotype-specific guidelines. Preliminary rules were tested by using a pilot set of 52 variants; among these, 50 were previously classified as benign/likely benign, pathogenic/likely pathogenic, variant of unknown significance (VUS), or conflicting interpretations (CONF) in ClinVar. The application of RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the benefit of gene-specific criteria and sharing internal laboratory data.

Published
2019
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12. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study

Author

Alexander C. Leeksma, Panagiotis Baliakas, Theodoros Moysiadis, Anna Puiggros, Karla Plevova, Anne-Marie van der Kevie-Kersemaekers, Hidde Posthuma, Ana E. Rodriguez-Vicente, Anh Nhi Tran, Gisela Barbany, Larry Mansouri, Rebeqa Gunnarsson, Helen Parker, Eva van den Berg, Mar Bellido, Zadie Davis, Meaghan Wall, Ilaria Scarpelli, Anders Österborg, Lotta Hansson, Marie Jarosova, Paolo Ghia, Pino Poddighe, Blanca Espinet, Sarka Pospisilova, Constantine Tam, Loïc Ysebaert, Florence Nguyen-Khac, David Oscier, Claudia Haferlach, Jacqueline Schoumans, Marian Stevens-Kroef, Eric Eldering, Kostas Stamatopoulos, Richard Rosenquist, Jonathan C. Strefford, Clemens Mellink, and Arnon P. Kater

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p

Published
2020
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13. Nordic Guidelines for Germline Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up

Author

Panagiotis Baliakas, Bianca Tesi, Ulla Wartiovaara-Kautto, Asbjørg Stray-Pedersen, Lone Smidstrup Friis, Ingunn Dybedal, Randi Hovland, Kirsi Jahnukainen, Klas Raaschou-Jensen, Per Ljungman, Cecilie F. Rustad, Charlotte K. Lautrup, Outi Kilpivaara, Astrid Olsnes Kittang, Kirsten Grønbæk, Jörg Cammenga, Eva Hellström-Lindberg, and Mette K. Andersen

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract. Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.

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

Author

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

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
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 SF3B1 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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15. 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

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

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2018
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17. ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset #2 is associated with markedly short telomeres

Author

Veronika Navrkalova, Emma Young, Panagiotis Baliakas, Lenka Radova, Lesley-Ann Sutton, Karla Plevova, Larry Mansouri, Viktor Ljungström, Stavroula Ntoufa, Zadie Davis, Gunnar Juliusson, Karin E. Smedby, Chrysoula Belessi, Panagiotis Panagiotidis, Tasoula Touloumenidou, Frederic Davi, Anton W. Langerak, Paolo Ghia, Jonathan C. Strefford, David Oscier, Jiri Mayer, Kostas Stamatopoulos, Sarka Pospisilova, Richard Rosenquist, and Martin Trbusek

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2016
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18. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

Author

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

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
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

Published
2016
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19. Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference

Author

Panagiotis Baliakas, Anna Puiggros, Aliki Xochelli, Lesley-Ann Sutton, Florence Nguyen-Khac, Anne Gardiner, Karla Plevova, Eva Minga, Anastasia Hadzidimitriou, Renata Walewska, Helen McCarthy, Margarita Ortega, Rosa Collado, Teresa González, Isabel Granada, Elisa Luño, Jana Kotašková, Theodoros Moysiadis, Zadie Davis, Niki Stavroyianni, Achilles Anagnostopoulos, Jonathan C. Strefford, Sarka Pospisilova, Frederic Davi, Anastasia Athanasiadou, Richard Rosenquist, David Oscier, Blanca Espinet, and Kostas Stamatopoulos

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2016
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21. Somatic Exonic Deletions in RUNX1 Constitutes a Novel Recurrent Genomic Abnormality in Acute Myeloid Leukemia

Author

Anna Eriksson, Marie Engvall, Lucy Mathot, Albin Österroos, Martin Rippin, Lucia Cavelier, Claes Ladenvall, and Panagiotis Baliakas

Subjects
Cancer Research, Oncology
Abstract

Purpose: In acute myeloid leukemia (AML), somatic mutations (commonly missense, nonsense, and frameshift indels) in RUNX1 are associated with a dismal clinical outcome. Inherited RUNX1 mutations cause familial platelet disorder. As approximately 5%–10% of germline RUNX1 mutations are large exonic deletions, we hypothesized that such exonic RUNX1 aberrations may also be acquired during the development of AML. Experimental Design: Sixty patients with well-characterized AML were analyzed with multiplex ligation-dependent probe amplification (n = 60), microarray (n = 11), and/or whole-genome sequencing (n = 8). Results: In total, 25 (42% of the cohort) RUNX1-aberrant patients (defined by the presence of classical mutations and/or exonic deletions) were identified. Sixteen patients (27%) carried only exonic deletions, 5 (8%) carried classical mutations, and 4 (7%) carried both exonic deletions and mutations. No significant difference was observed between patients with classical RUNX1 mutations and RUNX1 exonic deletions in median overall survival (OS, 53.1 vs. 38.8 months, respectively, P = 0.63). When applying the European Leukemia Net (ELN) classification including the RUNX1-aberrant group, 20% of the patients initially stratified as intermediate-risk (5% of the whole cohort) were reassigned to the high-risk group, which improved the performance of ELN classification regarding OS between intermediate- and high-risk groups (18.9 vs. 9.6 months, P = 0.09). Conclusions: Somatic RUNX1 exonic deletions constitute a novel recurrent aberration in AML. Our findings have important clinical implications regarding AML classification, risk stratification, and treatment decision. Moreover, they argue in favor of further investigating such genomic aberrations not only in RUNX1 but also in other genes implicated in cancer biology and management.

Published
2023

22. A Comprehensive DNA Methylome Analysis of Stereotyped and Non-Stereotyped CLL Reveals an Epigenetic Signature with Strong Clinical Impact Encompassing IGHV Status, Stereotypes and IGLV3-21R110

Author

Martí Duran-Ferrer, Larry Mansouri, Ferran Nadeu, Guillem Clot, Sujata Bhoi, Lesley Ann Sutton, Panagiotis Baliakas, Sara Ek, Venera Kuci Emruli, Karla Plevova, Zadie Davis, Hanna Goransson-Kultima, Anders Isaksson, Karin E. Smedby, Gianluca Gaidano, Anton W. Langerak, Frederic Davi, Davide Rossi, David Oscier, Sarka Pospisilova, Maria Karypidou, Andreas Agathangelidis, Wolfgang Huber, Junyan Lu, Thorsten Zenz, Julio Delgado, Armando Lopez-Guillermo, Paolo Ghia, Elías Campo, Kostas Stamatopoulos, Richard Rosenquist, and José I. Martín-Subero

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

26. Supplemental Table 5 from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

Recurrent amino acid replacements. Counts and distribution per IGHV gene and V-subregion. Respective physicochemical characteristics of the substitutions

Published
2023

27. Supplemental Table 2 from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

IGH rearrangements'intraclonal diversification characteristics. Counts, distribution, hotspot targeting of confirmed/unconfirmed mutations and respective amino acid changes across gene groups and IGHV subregions.

Published
2023

28. Figure S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

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

Abstract

Distribution of IGHV4-34 CLL according to IGHV mutational status and subset membership.

Published
2023

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

Author

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

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
2023

30. Data from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation.Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM).Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P = 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene).Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease. Clin Cancer Res; 22(8); 2032–40. ©2015 AACR.

Published
2023

31. Table S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

Author

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

Abstract

Univariable and multivariable analysis for TTFT within M-CLL.

Published
2023

32. Supplemental Table 1 from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

Analyzed IGH, IGK/L rearrangements. Annotation characteristics

Published
2023

33. Supplemental Figure 1 from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

Network of the aligned IGVH1-2*04 CDR3 sub-regions, depicting the emerging patterns

Published
2023

34. Supplemental Table 3 from An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

Author

Kostas Stamatopoulos, Anastasia Hadzidimitriou, Chrysoula Belessi, Dimitrios Tzovaras, Nikos Darzentas, David Oscier, Richard Rosenquist, Paolo Ghia, Theodora Papadaki, Miguel Angel Piris, Estella Matutes, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Manuela Mollejo, Alexandra Traverse-Glehen, George Kanellis, Patricia Algara, Zadie Davis, Evdoxia Papadopoulou, Andreas Agathangelidis, George Papadopoulos, Lesley-Ann Sutton, Aliki Xochelli, Panagiotis Baliakas, Evangelia Stalika, Maria Karypidou, and Vasilis Bikos

Abstract

IGK/L rearrangements'intraclonal diversification characteristics. Counts, distribution, hotspot targeting of confirmed/unconfirmed mutations and respective amino acid changes across gene groups and IGLV subregions.

Published
2023

35. International validation of the EORTC QLQ‐CLL17 questionnaire for assessment of health‐related quality of life for patients with chronic lymphocytic leukaemia

Author

Simone, Oerlemans, Fabio, Efficace, Jacobien M, Kieffer, Charalampia, Kyriakou, Aliki, Xochelli, Kerstin, Levedahl, Duska, Petranovic, Fabio Cardoso, Borges, Anne, Bredart, Omar, Shamieh, Laimonas, Gziskevicius, Jens, Lehmann, Christian W, Scholz, Giovanni, Caocci, Stefano, Molica, Kostas, Stamatopoulos, Alkistis-Kyra, Panteliadou, Maria, Papaioannou, Waleed, Alrjoob, Panagiotis, Baliakas, Richard, Rosenquist, Sandra, Malak, Ana, Miranda, Kim, Cocks, Lonneke, van de Poll-Franse, and Medical and Clinical Psychology

Subjects
PRO, Psychometrics, questionnaire, QLQ-C30, Pain, Reproducibility of Results, Hematology, FEAR, psychometric properties, Leukemia, Lymphocytic, Chronic, B-Cell, THERAPY, EORTC, TRIALS, quality of life, Surveys and Questionnaires, CHLORAMBUCIL, LYMPHOMA, Humans, CRITERIA, symptoms, REPORTED OUTCOMES, RITUXIMAB, chronic lymphocytic leukaemia
Abstract

Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient-reported health-related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ-CLL17 to supplement the core questionnaire (EORTC QLQ-C30). Patients with CLL (n = 341) from 12 countries completed the QLQ-C30, QLQ-CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%-66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test-retest and convergent validity was demonstrated. The QLQ-CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1-3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ-CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision-making.

Published
2022

36. Correction : Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Author

Larry Mansouri, Birna Thorvaldsdottir, Lesley-Ann Sutton, Georgios Karakatsoulis, Manja Meggendorfer, Helen Parker, Ferran Nadeu, Christian Brieghel, Stamatia Laidou, Riccardo Moia, Davide Rossi, Mark Catherwood, Jana Kotaskova, Julio Delgado, Ana E. Rodríguez-Vicente, Rocío Benito, Gian Matteo Rigolin, Silvia Bonfiglio, Lydia Scarfo, Mattias Mattsson, Zadie Davis, Ajay Gogia, Lata Rani, Panagiotis Baliakas, Hassan Foroughi-Asl, Cecilia Jylhä, Aron Skaftason, Inmaculada Rapado, Fatima Miras, Joaquín Martinez-Lopez, Javier de la Serna, Jesús María Hernández Rivas, Patrick Thornton, María José Larráyoz, María José Calasanz, Viktória Fésüs, Zoltán Mátrai, Csaba Bödör, Karin E. Smedby, Blanca Espinet, Anna Puiggros, Ritu Gupta, Lars Bullinger, Francesc Bosch, Bárbara Tazón-Vega, Fanny Baran-Marszak, David Oscier, Florence Nguyen-Khac, Thorsten Zenz, Maria Jose Terol, Antonio Cuneo, María Hernández-Sánchez, Sarka Pospisilova, Ken Mills, Gianluca Gaidano, Carsten U. Niemann, Elias Campo, Jonathan C. Strefford, Paolo Ghia, Kostas Stamatopoulos, and Richard Rosenquist

Subjects
Cancer Research, Oncology, Genetics research, Hematology, Cancer genetics
Published
2023

37. BTK and PLCG2 remain unmutated in one third of patients with CLL relapsing on ibrutinib

Author

Silvia Bonfiglio, Lesley-Ann Sutton, Viktor Ljungström, Antonella Capasso, Tatjana Pandzic, Simone Weström, Hassan Foroughi-Asl, Aron Skaftason, Anna Gellerbring, Anna Lyander, Francesca Gandini, Gianluca Gaidano, Livio Trentin, Lisa Bonello, Gianluigi Reda, Csaba Bödör, Niki Stavroyianni, Constantine S. Tam, Roberto Marasca, Francesco Forconi, Panayiotis Panayiotidis, Ingo Ringshausen, Ozren Jaksic, Anna Maria Frustaci, Sunil Iyengar, Marta Coscia, Stephen P. Mulligan, Loïc Ysebaert, Vladimir Strugov, Carolina Pavlovsky, Renata Walewska, Anders Österborg, Diego Cortese, Pamela Ranghetti, Panagiotis Baliakas, Kostas Stamatopoulos, Lydia Scarfò, Richard Rosenquist, and Paolo Ghia

Subjects
Hematology
Abstract

Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet clinical need. Though BTK and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL treated with ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital PCR (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32/49 relapsing cases (65%) carried at least 1 hotspot BTK mutation and/or PLCG2 mutation(s); in 6/32, BTK mutations were only detected by ddPCR [variant allele frequency (VAF) 0.1-1.2%]. BTK/PLCG2 mutations were also identified in 6/49 responding patients (12%; 5/6 VAF

Published
2023

38. Familial platelet disorder due to germline exonic deletions in

Author

Marie, Engvall, Ylva, Karlsson, Ekaterina, Kuchinskaya, Åsa, Jörnegren, Lucy, Mathot, Tatjana, Pandzic, Josefine, Palle, Viktor, Ljungström, Lucia, Cavelier, Eva, Hellström Lindberg, Jörg, Cammenga, and Panagiotis, Baliakas

Subjects
Leukemia, Myeloid, Acute, Germ Cells, Core Binding Factor Alpha 2 Subunit, Humans, Protein Isoforms, Blood Platelet Disorders, Exons
Abstract

Germline pathogenic variants in

Published
2022

40. Higher-order connections between stereotyped subsets

Author

Andrea Patriarca, Marco Montillo, Niki Stavroyianni, Claudia Haferlach, Lesley-Ann Sutton, Livio Trentin, Franco Fais, Raphael Sandaltzopoulos, Arnon P. Kater, Anton W. Langerak, Marine Armand, Davide Rossi, Diane F. Jelinek, Davide Bagnara, Lydia Scarfò, Andreas Agathangelidis, Krzysztof Giannopoulos, Eugen Tausch, Andrey Sudarikov, Silvio Veronese, Salem H. Alshemmari, B V Biderman, Zadie Davis, Chrysoula Belessi, Lisa Bonello, Achilles Anagnostopoulos, Gerlinde Mitterbauer-Hohendanner, David Oscier, Sofia Kossida, Lone Bredo Pedersen, Paolo Ghia, Csaba Bödör, Christian Brieghel, Andrea Visentin, Véronique Giudicelli, Matthias Ritgen, Panagiotis Panagiotidis, Panagiotis Baliakas, Stephan Stilgenbauer, Ellen J van Gastel, Renee C. Tschumper, Christiane Pott, Frederic Davi, Katerina Gemenetzi, Valentina Guido, Elias Campo, Gianluca Gaidano, Irina Panovska, Sabine Jeromin, Karla Plevová, Kostas Stamatopoulos, Kamila Brázdilová, Maria Karypidou, Alba Navarro, Christof W. Schneider, Theodoros Moysiadis, Larry Mansouri, Darko Antic, Cristina Tresoldi, Constance Baer, Šárka Pospíšilová, Maria Roumelioti, Katrina Vanura, Xiao-Jie Yan, Hana Skuhrová Francová, Richard Rosenquist, Blanca Espinet, Paola Francia di Celle, Monica Facco, Paul Costeas, Michael Hallek, Carsten Utoft Niemann, Teodora Karan-Djurasevic, Manja Meggendorfer, Kirsten Fischer, Aleksandar Dimovski, Letizia Foroni, Marie-Paule Lefranc, Mark Catherwood, Anne de Septenville, Anastasia Chatzidimitriou, Sarah Lawless, Nicholas Chiorazzi, Agathangelidis, Andrea, Chatzidimitriou, Anastasia, Gemenetzi, Katerina, Giudicelli, Veronique, Karypidou, Maria, Plevova, Karla, Davis, Zadie A, Yan, Xiao-Jie, Jeromin, Sabine, Schneider, Christof, Pedersen, Lone Bredo, Tschumper, Renee, Sutton, Lesley A, Baliakas, Panagioti, Scarfò, Lydia, van Gastel, Ellen J, Armand, Marine, Tausch, Eugen, Biderman, Bella, Baer, Constance, Bagnara, Davide, Navarro, Alba, de Septenville, Anne, Guido, Valentina, Mitterbauer-Hohendanner, Gerlinde, Dimovski, Aleksandar, Brieghel, Christian, Lawless, Sarah, Meggendorfer, Manja, Stranska, Kamila, Ritgen, Matthia, Facco, Monica, Tresoldi, Cristina, Visentin, Andrea, Patriarca, Andrea, Catherwood, Mark, Bonello, Lisa, Sudarikov, Andrey, Vanura, Katrina, Roumelioti, Maria, Skuhrova Francova, Hana, Moysiadis, Theodoro, Veronese, Silvio M, Giannopoulos, Krzysztof, Mansouri, Larry, Karan-Djurasevic, Teodora, Sandaltzopoulos, Raphael, Bödör, Csaba, Fais, Franco, Kater, Arnon P, Panovska-Stavridis, Irina, Rossi, Davide, Alshemmari, Salem, Panagiotidis, Panagioti, Costeas, Paul A, Espinet, Blanca, Antic, Darko, Foroni, Letizia, Montillo, Marco, Trentin, Livio, Stavroyianni, Niki, Gaidano, Gianluca, Francia di Celle, Paola, Niemann, Carsten Utoft, Campo, Elía, Anagnostopoulos, Achille, Pott, Christiane, Fischer, Kirsten, Hallek, Michael, Oscier, David Graham, Stilgenbauer, Stephan, Haferlach, Claudia, Jelinek, Diane F, Chiorazzi, Nichola, Pospisilova, Sarka, Lefranc, Marie-Paule, Kossida, Sofia, Langerak, Anton W, Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, Experimental Immunology, Clinical Haematology, AII - Cancer immunology, CCA - Cancer biology and immunology, and Immunology

Subjects
Chronic lymphocytic leukemia, Immunology, B-cell receptor, Immunoglobulin Variable Region, Disease, Computational biology, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, hemic and lymphatic diseases, Immunoglobulin, medicine, Humans, Chronic, 030304 developmental biology, Gene Rearrangement, 0303 health sciences, Leukemia, Lymphoid Neoplasia, Repertoire, B-Cell, breakpoint cluster region, Cell Biology, Hematology, Gene rearrangement, Somatic Hypermutation, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphocytic, Stereotypy (non-human), Immunoglobulin Heavy Chains, Somatic Hypermutation, Immunoglobulin, 030220 oncology & carcinogenesis, IGHV@
Abstract

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

Published
2021

41. Early response evaluation by single cell signaling profiling in acute myeloid leukemia

Author

Tislevoll, Benedicte, primary, Hellesøy, Monica, additional, Fagerholt, Oda, additional, Gullaksen, Stein-Erik, additional, Srivast, Aashish, additional, Birkeland, Even, additional, Kleftogiannis, Dimitrios, additional, Ayuda-Durán, Pilar, additional, Piechaczyk, Laure, additional, Tadele, Dagim, additional, Skavland, Jørn, additional, Panagiotis, Baliakas, additional, Hovland, Randi, additional, Andresen, Vibeke, additional, Aghaeepour, Nima, additional, Gavasso, Sonia, additional, Porkka, Kimmo, additional, Jonassen, Inge, additional, Enserink, Jorrit, additional, Fløisand, Yngvar, additional, Blaser, Nello, additional, and Gjertsen, Björn Tore, additional

Published
2022
Full Text
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42. Familial platelet disorder due to germline exonic deletions in RUNX1 : a diagnostic challenge with distinct alterations of the transcript isoform equilibrium

Author

Marie Engvall, Ylva Karlsson, Ekaterina Kuchinskaya, Åsa Jörnegren, Lucy Mathot, Tatjana Pandzic, Josefine Palle, Viktor Ljungström, Lucia Cavelier, Eva Hellström Lindberg, Jörg Cammenga, and Panagiotis Baliakas

Subjects
Cancer Research, Oncology, FPD, hemic and lymphatic diseases, leukemia, RUNX1 deletions, thrombocytopenia, MM, Hematology, Hematologi
Abstract

Germline pathogenic variants in RUNX1 are associated with familial platelet disorder with predisposition to myeloid malignancies (FPD/MM) with intragenic deletions in RUNX1 accounting for almost 7% of all reported variants. We present two new pedigrees with FPD/MM carrying two different germline RUNX1 intragenic deletions. The aforementioned deletions encompass exons 1-2 and 9-10 respectively, with the exon 9-10 deletion being previously unreported. RNA sequencing of patients carrying the exon 9-10 deletion revealed a fusion with LINC00160 resulting in a change in the 3 sequence of RUNX1. Expression analysis of the transcript isoform demonstrated altered RUNX1a/b/c ratios in carriers from both families compared to controls. Our data provide evidence on the impact of intragenic RUNX1 deletions on transcript isoform expression and highlight the importance of routinely performing copy number variant analysis in patients with suspected MM with germline predisposition. Funding Agencies|Lions Cancer Research Foundation, Uppsala

Published
2022

43. Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy

Author

Maria‐Teresa Voso, Tatjana Pandzic, Giulia Falconi, Marija Denčić‐Fekete, Eleonora De Bellis, Lydia Scarfo, Viktor Ljungström, Michail Iskas, Giovanni Del Poeta, Pamela Ranghetti, Stamatia Laidou, Antonio Cristiano, Karla Plevova, Silvia Imbergamo, Marie Engvall, Antonella Zucchetto, Chiara Salvetti, Francesca R. Mauro, Niki Stavroyianni, Lucia Cavelier, Paolo Ghia, Kostas Stamatopoulos, Emiliano Fabiani, Panagiotis Baliakas, Voso, M. -T., Pandzic, T., Falconi, G., Dencic-Fekete, M., De Bellis, E., Scarfo, L., Ljungstrom, V., Iskas, M., Del Poeta, G., Ranghetti, P., Laidou, S., Cristiano, A., Plevova, K., Imbergamo, S., Engvall, M., Zucchetto, A., Salvetti, C., Mauro, F. R., Stavroyianni, N., Cavelier, L., Ghia, P., Stamatopoulos, K., Fabiani, E., and Baliakas, P.

Subjects
t-MN, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Mutation, Humans, Neoplasms, Second Primary, Hematology, Clonal Hematopoiesis, Settore MED/15, Leukemia, Lymphocytic, Chronic, B-Cell, CLL, CHIP and FCR
Abstract

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0–6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1–5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p=0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.

Published
2021

44. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Author

Ellen van der Spek, Emili Montserrat, Talha Munir, Paolo Ghia, Shaimaa El-Ashwah, Andreas Glenthøj, Viola Maria Popov, Sanne H. Tonino, Ann Janssens, Michel van Gelder, Lara Malerba, Rocío García-Serra, Alberto Lopez-Garcia, Juan-Gonzalo Correa, Christos Demosthenous, Idanna Innocenti, Maria Papaioannou, Lydia Scarfò, Antonio Cuneo, Francesca Romana Mauro, Sabina Kersting, Robin Foà, David Donaldson, Livio Trentin, Roberta Murru, Panagiotis Baliakas, Marina Motta, Deepesh Lad, Yervand K Hakobyan, Paolo Sportoletti, Lucrecia Yáñez San Segundo, Alicia Enrico, Elżbieta Kalicińska, Ewa Wasik-Szczepanek, Martin Spacek, Tamar Tadmor, Enrico Lista, Roel van Kampen, Lorella Orsucci, Michael Doubek, Yair Herishanu, Blanca Espinet, Jose Angel Hernandez-Rivas, Inga Piskunova, Ozren Jakšić, Georgios Karakatsoulis, Tomasz Wróbel, Oana Stanca, Luca Laurenti, Martin Andres, Roberto Marasca, Mark-David Levin, Giovanni Del Poeta, Miguel Arturo Pavlovsky, Maria Dimou, Monia Marchetti, Ivana Milosevic, Gianluigi Reda, Tobias Herold, David Allsup, Raul Cordoba, Andrea Visentin, Maria Gomes da Silva, Angela Ferrari, Antonella Capasso, Juan Marquet, Francesca Maria Quaglia, Candida Vitale, Mattias Mattsson, Marta Coscia, Moritz Fürstenau, Lucia Farina, Niki Stavroyianni, Marta Morawska, Arnon P. Kater, Mónica Baile, Gevorg Saghumyan, Carolina Cuéllar-García, Jacopo Olivieri, Darko Antic, Raquel Nunes Rodrigues, Alejandro Alonso Cabrero, Henrik Frederiksen, Alessandro Rambaldi, Marzia Varettoni, Amit Shrestha, Оlga B Kalashnikova, Thomas Chatzikonstantinou, José A. García-Marco, Martin Simkovic, Linda Katharina Karlsson, Odit Gutwein, Mohamed A. Yassin, Rosa Ruchlemer, Eva Gimeno, Kristian Qvist, Fatima Miras, Gilad Itchaki, Maria Rosaria De Paolis, Maria Efstathopoulou, Doreen te Raa, Barbara Eichhorst, Dominique Bron, Jorge Labrador, Gian Matteo Rigolin, Myriam Foglietta, Massimo Gentile, Sofia Chatzileontiadou, Carsten Utoft Niemann, Anargyros Kapetanakis, Kostas Stamatopoulos, Lorenzo De Paoli, Giulia Quaresmini, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), Chatzikonstantinou, T., Kapetanakis, A., Scarfo, L., Karakatsoulis, G., Allsup, D., Cabrero, A. A., Andres, M., Antic, D., Baile, M., Baliakas, P., Bron, D., Capasso, A., Chatzileontiadou, S., Cordoba, R., Correa, J. -G., Cuellar-Garcia, C., De Paoli, L., De Paolis, M. R., Del Poeta, G., Demosthenous, C., Dimou, M., Donaldson, D., Doubek, M., Efstathopoulou, M., Eichhorst, B., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Frederiksen, H., Furstenau, M., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, M., Gimeno, E., Glenthoj, A., Gomes da Silva, M., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Innocenti, I., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, Оb., Kalicinska, E., Karlsson, L. K., Kater, A. P., Kersting, S., Labrador, J., Lad, D., Laurenti, L., Levin, M. -D., Lista, E., Lopez-Garcia, A., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mattsson, M., Mauro, F. R., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Niemann, C. U., Rodrigues, R. N., Olivieri, J., Orsucci, L., Papaioannou, M., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Qvist, K., Reda, G., Rigolin, G. M., Ruchlemer, R., Saghumyan, G., Shrestha, A., Simkovic, M., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Tadmor, T., Te Raa, D., Tonino, S. H., Trentin, L., Van Der Spek, E., van Gelder, M., van Kampen, R., Varettoni, M., Visentin, A., Vitale, C., Wasik-Szczepanek, E., Wrobel, T., San Segundo, L. Y., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Stamatopoulos, K., Ghia, P., Experimental Immunology, Clinical Haematology, AII - Cancer immunology, and CCA - Cancer Treatment and Quality of Life

Subjects
Chronic lymphocytic leukaemia, Cancer Research, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Epidemiology, medicine.medical_treatment, Chronic lymphocytic leukemia, CLL, COVID-19, 610 Medicine & health, Disease, Lower risk, COVID-19 (Malaltia), Severity of Illness Index, Article, NO, law.invention, Risk Factors, law, Internal medicine, Case fatality rate, Mortalitat, medicine, Humans, Hematologi, Chronic, Mortality, Science & Technology, Leukemia, SARS-CoV-2, business.industry, Vaccination, B-Cell, Leucèmia, COVID-19, Immunosuppression, Hematology, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Intensive care unit, Lymphocytic, Oncology, business, Life Sciences & Biomedicine
Abstract

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p

Published
2021

45. Landscape of TP53 Alterations in Chronic Lymphocytic Leukemia

Author

Thierry, Soussi and Panagiotis, Baliakas

Abstract

Locus-specific databases are invaluable tools for both basic and clinical research. The extensive information they contain is gathered from the literature and manually curated by experts. Cancer genome sequencing projects generate an immense amount of data, which are stored directly in large repositories (cancer genome databases). The presence of a

Published
2021

46. Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

Author

Panagiotis, Baliakas, Blanca, Espinet, Clemens, Mellink, Marie, Jarosova, Anastasia, Athanasiadou, Paolo, Ghia, Arnon P, Kater, David, Oscier, Claudia, Haferlach, and Kostas, Stamatopoulos

Abstract

Mounting evidence underscores the clinical value of cytogenetic analysis in chronic lymphocytic leukemia (CLL), particularly as it allows the identification of complex karyotype, that has recently emerged as a prognostic and potentially predictive biomarker. That said, explicit recommendations regarding the methodology and clinical interpretation of either chromosome banding analysis (CBA) or chromosome microarray analysis (CMA) are still lacking. We herein present the consensus of the Cytogenetic Steering Scientific Committee of ERIC, the European Research Initiative on CLL, regarding methodological issues as well as clinical interpretation of CBA/CMA and discuss their relevance in CLL. ERIC considers CBA standardized and feasible for CLL on the condition that standards are met, extending from the use of novel mitogens to the accurate interpretation of the findings. On the other hand, CMA, is also standardized, however, robust data on its clinical utility are still scarce. In conclusion, cytogenetic analysis is not yet mature enough to guide treatment choices in CLL. That notwithstanding, ERIC encourages the wide application of CBA, and potentially also CMA, in clinical trials in order to obtain robust evidence regarding the predictive value of specific cytogenetic profiles towards refining risk stratification and improving the management of patients with CLL.

Published
2021

47. Early response evaluation by single cell signaling profiling in acute myeloid leukemia.

Author

Tislevoll, Benedicte Sjo, Hellesøy, Monica, Fagerholt, Oda Helen Eck, Gullaksen, Stein-Erik, Srivastava, Aashish, Birkeland, Even, Kleftogiannis, Dimitrios, Ayuda-Durán, Pilar, Piechaczyk, Laure, Tadele, Dagim Shiferaw, Skavland, Jørn, Panagiotis, Baliakas, Hovland, Randi, Andresen, Vibeke, Seternes, Ole Morten, Tvedt, Tor Henrik Anderson, Aghaeepour, Nima, Gavasso, Sonia, Porkka, Kimmo, and Jonassen, Inge

Subjects
ACUTE myeloid leukemia, CELL communication, MITOGEN-activated protein kinases, PROTEIN kinases, INDUCTION chemotherapy, SUPERVISED learning
Abstract

Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing shows induction of MAPK target gene expression in patients with high phospho-ERK1/2 24 h post-chemotherapy, while proteomics confirm an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics. The molecular mechanisms underlying response to chemotherapy in Acute myeloid leukemia (AML) remain to be explored. Here, the authors perform 36-dimensional mass cytometry in 32 AML patients during intensive chemotherapy and suggest functional signalling analysis for prognosis prediction early after treatment in AML. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Loss of Y and clonal hematopoiesis in blood-two sides of the same coin?

Author

Viktor, Ljungström, Jonas, Mattisson, Jonatan, Halvardson, Tatjana, Pandzic, Hanna, Davies, Edyta, Rychlicka-Buniowska, Marcus, Danielsson, Paul, Lacaze, Lucia, Cavelier, Jan P, Dumanski, Panagiotis, Baliakas, and Lars A, Forsberg

Subjects
Aged, 80 and over, Male, Aging, Chromosomes, Human, Y, Humans, Chromosome Deletion, Clonal Hematopoiesis, Monocytes, Aged
Published
2021

49. Different time-dependent changes of risk for evolution in chronic lymphocytic leukemia with mutated or unmutated antigen B cell receptors

Author

Richard Rosenquist, Mark Catherwood, Šárka Pospíšilová, Davide Rossi, Jonathan C. Strefford, Niki Stavroyianni, Gianluca Gaidano, Kostas Stamatopoulos, Theodoros Moysiadis, Achilles Anagnostopoulos, David Oscier, Chrysoula Belessi, Panagiotis Baliakas, Elias Campo, Paolo Ghia, Julio Delgado, Moysiadis, T., Baliakas, P., Rossi, D., Catherwood, M., Strefford, J. C., Delgado, J., Anagnostopoulos, A., Belessi, C., Stavroyianni, N., Pospisilova, S., Oscier, D., Gaidano, G., Campo, E., Rosenquist, R., Ghia, P., and Stamatopoulos, K.

Subjects
0301 basic medicine, Cancer Research, business.industry, Chronic lymphocytic leukemia, Antigen b, Hematology, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Text mining, Oncology, immune system diseases, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Immunology, Clinical heterogeneity, SURVIVAL, medicine, business, Receptor
Abstract

Chronic lymphocytic leukemia (CLL) displays remarkable clinical heterogeneity, likely attributed to the underlying biological diversity. This claim is supported by the fact that certain immunogenetic and/or genomic features identify subgroups of CLL patients with distinct prognosis and outcome.

Published
2019

50. Prognostic and Predictive Implications of Cytogenetics and Genomics

Author

Panagiotis Baliakas and Viktor Ljungström

Subjects
Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, Genomics, Prognostication, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, In patient, neoplasms, Chromosome Aberrations, Cancer och onkologi, business.industry, Cytogenetics, Hematology, medicine.disease, Prognosis, Predictive value, Leukemia, Lymphocytic, Chronic, B-Cell, Clinical trial, Novel agents, 030220 oncology & carcinogenesis, Cancer and Oncology, Cytogenetic Analysis, business, Prediction, CLL, 030215 immunology
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by extreme genomic heterogeneity. Numerous recurrent genetic abnormalities are associated with dismal clinical outcome in patients treated with chemo(immuno)therapy, with aberrations of the TP53 gene being the main genomic abnormalities that dictate treatment choice. In the era of novel agents the predictive significance of the genomic aberrations is highly challenged as the results of the clinical trials performed thus far question the previously established unfavorable impact of genomic aberrations, even that of the TP53 gene. The prognostic and predictive value of the most common genomic abnormalities is discussed in the present review.

Published
2021

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