Review
Oncology
Billy Michael Chelliah Jebaraj, Stephan Stilgenbauer
Summary: Telomeres play a crucial role in chronic lymphocytic leukemia (CLL), with their dysfunction shaping the disease progression. Members of the shelterin complex and TERT activation are closely associated with CLL cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Chi-Ling Chiang, Eileen Y. Hu, Lingqian Chang, Jadwiga Labanowska, Kevan Zapolnik, Xiaokui Mo, Junfeng Shi, Tzyy-Jye Doong, Arletta Lozanski, Pearlly S. Yan, Ralf Bundschuh, Logan A. Walker, Daniel Gallego-Perez, Wu Lu, Meixiao Long, Sanggu Kim, Nyla A. Heerema, Gerard Lozanski, Jennifer A. Woyach, John C. Byrd, Ly James Lee, Natarajan Muthusamy
Summary: This study used a microchannel electroporation technique to investigate the hematopoietic stem cells in chronic lymphocytic leukemia, confirming the existence of clonal hematopoietic stem cells and their differential drug sensitivity. Furthermore, the existence of CLL LICs was validated in both patient and mouse models. Additionally, differential protein ubiquitination and unfolding response were found in GATA2(high) CLL-HSCs, which significantly affected drug sensitivity.
Article
Oncology
Elisavet Vlachonikola, Nikolaos Pechlivanis, Georgios Karakatsoulis, Electra Sofou, Glykeria Gkoliou, Sabine Jeromin, Niki Stavroyianni, Pamela Ranghetti, Lydia Scarfo, Cecilia Osterholm, Larry Mansouri, Sofia Notopoulou, Alexandra Siorenta, Achilles Anagnostopoulos, Paolo Ghia, Claudia Haferlach, Richard Rosenquist, Fotis Psomopoulos, Anastasia Kouvatsi, Panagiotis Baliakas, Kostas Stamatopoulos, Anastasia Chatzidimitriou
Summary: Microenvironmental interactions between the malignant clone and T cells are crucial in the development of CLL. The study identifies distinct T cell receptor profiles in patients with different genomic aberrations, suggesting different selection processes. Abnormal protein expression and gene dosage effects from recurrent genomic aberrations may provide CLL-specific antigens for T cells.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Vivian-Pascal Brandt, Heidrun Holland, Marco Wallenborn, Ronald Koschny, Clara Frydrychowicz, Mandy Richter, Lydia Holland, Ulf Nestler, Caroline Sander
Summary: Brain metastases in colorectal cancer patients are rare and associated with poor survival. Chromosomal aberrations, particularly cn-LOHs, are more frequent in brain metastases compared to primary tumors and liver metastases, shedding light on the pathophysiology of brain metastasis formation. Further genetic analyses between primary tumors and metastases are needed to define the role of affected genes in cn-LOH regions.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Anna Grenda, Agata A. Filip, Ewa Wasik-Szczepanek
Summary: The study found that the expression levels of miRNA-181a, -221, and -223 are closely related to the risk of disease progression in CLL patients; miRNA-181b and -223 are expressed at higher levels in patients without D13S319 deletion; patients with CLL who have a tumor protein p53 deletion show higher expression levels of miR-15a and miRNA-29c.
MOLECULAR MEDICINE REPORTS
(2022)
Review
Oncology
Adalgisa Condoluci, Davide Rossi
Summary: Genomic instability and clonal heterogeneity in CLL play a crucial role in cancer progression, treatment response, and refractoriness. Different clonal evolution patterns provide insights into disease dynamics, selection, and targeted therapy strategies.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
Review
Oncology
Marwan Kwok, Catherine J. Wu
Summary: In recent years, there have been significant advancements in our understanding of clonal evolution in high-risk CLL, highlighting recent discoveries, paradigm shifts, and unresolved questions. These advancements have been facilitated by a maturing definition of high-risk CLL and an increasing sophistication of next-generation sequencing technology.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
John Mollstedt, Larry Mansouri, Richard Rosenquist
Summary: Genetic diagnostics of hematological malignancies has advanced from chromosomal banding analysis to next-generation sequencing, allowing for the detection of clinically relevant biomarkers. In chronic lymphocytic leukemia (CLL) patients, fluorescence in situ hybridization (FISH) and targeted sequencing are used for diagnosis and risk-stratification. This review provides an update on the genomic landscape of CLL and discusses state-of-the-art technologies for precision diagnostics, as well as the potential of new technologies for subclassification and precision medicine.
FRONTIERS IN ONCOLOGY
(2023)
Article
Hematology
Marc Zapatka, Eugen Tausch, Selcen Oeztuerk, Deyan Yordanov Yosifov, Martina Seiffert, Thorsten Zenz, Christof Schneider, Johannes Bloehdorn, Hartmut Doehner, Daniel Mertens, Peter Lichter, Stephan Stilgenbauer
Summary: Clonal evolution plays a significant role in the progression of CLL. Long-term longitudinal mutation profiling study revealed distinct evolutionary patterns, with minor clonal shifts in stable disease and relapse after long-lasting treatment response, but major clonal shifts in refractory disease. These shifts are not strongly linked to known CLL driver genes, suggesting that they are mostly driven by treatment-induced selection of sub-clones, highlighting the need for novel non-genotoxic treatment regimens.
Article
Hematology
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 Osterborg, Lotta Hansson, Marie Jarosova, Paolo Ghia, Pino Poddighe, Blanca Espinet, Sarka Pospisilova, Constantine Tam, Loic Ysebaert, Florence Nguyen-Khac, David Oscier, Claudia Haferlach, Jacqueline Schoumans, Marian Stevens-Kroef, Eric Eldering, Kostas Stamatopoulos, Richard Rosenquist, Jonathan C. Strefford, Clemens Mellink, Arnon P. Kater
Summary: Genomic arrays have been shown to be an accurate tool for risk stratification in CLL, with high genomic complexity being an independent adverse prognosticator. Lowering the size cutoff for CNA did not significantly improve risk assessment. Arrays detected more chromosomal abnormalities and performed at least as well as simultaneous chromosome banding analysis for risk stratification.
Review
Oncology
Paulina Stefaniuk, Julia Onyszczuk, Agnieszka Szymczyk, Monika Podhorecka
Summary: CLL, the most common type of leukemia in adults in western countries, shows heterogeneity in clinical course and response to treatment. TP53 aberrations are the most important factors of poor prognosis. Treatment of patients with TP53-deficiency requires drugs promoting cell death independently of TP53.
CANCER MANAGEMENT AND RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kristan V. Piroeva, Charlotte Mcdonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe, Vladimir B. Teif
Summary: This study compared the nucleosome positions in chronic lymphocytic leukemia (CLL) patients and healthy individuals, and found significant changes in nucleosome positioning in CLL. The spacing between nucleosomes was shortened, and changes in nucleosome occupancy were linked to chromatin remodeling and reduced DNA methylation. Nucleosome positioning can be used to classify CLL subtypes and monitor disease progression.
Review
Oncology
Idanna Innocenti, Giulia Benintende, Annamaria Tomasso, Alberto Fresa, Francesco Autore, Luigi Maria Larocca, Luca Laurenti
Summary: Chronic lymphocytic leukemia can transform into an aggressive lymphoma called Richter syndrome. Immunogenotypic features of Richter syndrome include unmutated IgHV status, deletion of chromosome 17p or 11q, activation of oncogenes, and inactivation of onco-suppressors. The prognosis for patients with Richter syndrome is very poor, and current treatment options are limited. Understanding the biology of this condition is crucial for personalized treatment and improving survival.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Menna Al-Adl, Afaf El-Said, Ahmed EL-Sebaie, Sherif Refaat, Magdy M. Youssef
Summary: This study found that the CYP1A1*2A (T3801C, rs4646903) single nucleotide polymorphism (SNP) may be a risk factor for developing B-CLL, and the impact of this SNP on the disease progression and the clinical outcome.
Article
Oncology
Anneke D. van Dijk, Ti'ara L. Griffen, Yihua H. Qiu, Fieke W. Hoff, Endurance Toro, Kevin Ruiz, Peter P. Ruvolo, James W. Lillard, Eveline S. J. M. de Bont, Jan A. Burger, William Wierda, Steven M. Kornblau
Summary: In this study, four epigenetically distinct proteomic signatures associated with clinical features and outcome measures were identified in a large cohort of CLL and related diseases derived samples using reverse phase protein array technology. These protein signatures were found to be predictive markers for overall survival independent of other clinical features. Among the analyzed epigenetic proteins, EZH2, HDAC6, and loss of H3K27me3 levels were found to be most independently associated with poor survival. This demonstrates the potential of proteomic based epigenetic biomarkers in better classifying and guiding treatment for CLL patients.
Review
Oncology
Manja Meggendorfer, Vaidehi Jobanputra, Kazimierz O. Wrzeszczynski, Paul Roepman, Ewart de Bruijn, Edwin Cuppen, Reinhard Buttner, Carlos Caldas, Sean Grimmond, Charles G. Mullighan, Olivier Elemento, Richard Rosenquist, Anna Schuh, Torsten Haferlach
Summary: Interrogating the tumor genome through whole-genome sequencing (WGS) has the potential to impact cancer diagnostics, prognostication, and therapy selection. This review emphasizes the requirements for implementing, validating, and maintaining a clinical WGS pipeline to obtain high-quality patient-specific data.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Aron Skaftason, Ying Qu, Maysaa Abdulla, Jessica Nordlund, Mattias Berglund, Susanne Bram Ednersson, Per-Ola Andersson, Gunilla Enblad, Rose-Marie Amini, Richard Rosenquist, Larry Mansouri
Summary: This study used an exome capture-based RNA-sequencing protocol to explore gene expression in FF and FFPE samples from DLBCL patients, finding that despite fewer mapped reads, FFPE samples maintained similar gene expression to FF samples. Through clustering analysis and validation cohorts, the high consistency in gene expression between FF and FFPE samples was confirmed.
GENES CHROMOSOMES & CANCER
(2022)
Review
Medicine, General & Internal
Marco M. Buhler, Jose Martin-Subero, Qiang Pan-Hammarstrom, Elias Campo, Richard Rosenquist
Summary: Histopathologic examination is important for the diagnosis of lymphoid malignancies, but recent advances in high-throughput technologies have improved our understanding of these tumors. Certain genomic alterations can provide diagnostic information and others can indicate prognosis or treatment response. Comprehensive molecular profiling may pave the way for precision diagnostics and medicine.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Oncology
Larry Mansouri, Birna Thorvaldsdottir, Stamatia Laidou, Kostas Stamatopoulos, Richard Rosenquist
Summary: Genetics plays a crucial role in the clinical diagnostics of lymphomas, helping to subclassify the disease and stratify patient risk. Recent advancements in high-throughput sequencing technologies have provided a detailed understanding of the genomic landscape of various lymphoma entities, revealing a diverse genetic background. These studies have improved our understanding of lymphoma ontogeny and evolution and have identified potential genetic markers that can enhance lymphoma diagnostics and prognostication. However, the number of gene mutations with predictive impact for treatment selection remains limited. This review highlights clinically relevant diagnostic, prognostic, and predictive markers in lymphomas and discusses the potential of comprehensive genomic characterization for precision diagnostics and tailored therapy strategies.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Hematology
Joel Joelsson, Tove Wasterlid, Richard Rosenquist, Lasse Hjort Jakobsen, Tarec C. El-Galaly, Karin E. Smedby, Sandra Eloranta
Summary: Considering the changes in treatment and prognosis for non-Hodgkin lymphoma (NHL), understanding long-term health outcomes and treatment-related complications has become increasingly important. This study investigates the time trends of second primary malignancies (SPMs) in Swedish NHL patients, both before and after the introduction of anti-CD20 antibody therapy. The findings indicate that NHL survivors have a higher risk of solid tumors and hematologic malignancies, particularly myelodysplastic syndrome/acute myeloid leukemia. The study also suggests that modern treatment standards are not associated with modified SPM risk, but nonchemotherapy-based treatments may help reduce the risk of myelodysplastic syndrome/acute myeloid leukemia in follicular lymphoma patients.
Article
Hematology
Eugen Tausch, Viktor Ljungstrom, Andreas Agathangelidis, Marc Zapatka, Lydia Scarfo, Billy Michael Chelliah Jebaraj, Deyan Y. Yosifov, Annika Mueller, Veerendra Munugalavadla, Jeremiah D. Degenhardt, Paolo Ghia, Richard Rosenquist, Stephan Stilgenbauer
Article
Hematology
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
Summary: This international study tested the psychometric properties of a newly developed measure for CLL patients and found that it can increase sensitivity of HRQoL assessment and provide better guidance for treatment decision-making.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Oncology
Andreas Agathangelidis, Anastasia Chatzidimitriou, Thomas Chatzikonstantinou, Cristina Tresoldi, Zadie Davis, Veronique Giudicelli, Sofia Kossida, Chrysoula Belessi, Richard Rosenquist, Paolo Ghia, Anton W. Langerak, Frederic Davi, Kostas Stamatopoulos
Summary: The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is critical for assessing prognosis and responses to therapy in patients with chronic lymphocytic leukemia (CLL). Immunogenetic analysis in CLL has also revealed distinct subsets of patients based on (quasi)identical B cell receptor immunoglobulin (BcR IG), which display consistent biology, clinical presentation, and outcome. As a cornerstone for accurate risk stratification and clinical decision making, immunogenetic analysis in CLL requires robust methodologies, including next generation sequencing (NGS).
Editorial Material
Oncology
Richard Rosenquist, Stefan Frohling, Kostas Stamatopoulos
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Medicine, General & Internal
Eva Berglund, Gisela Barbany, Christina Orsmark-Pietras, Linda Fogelstrand, Jonas Abrahamsson, Irina Golovleva, Helene Hallbook, Martin Hoglund, Vladimir Lazarevic, Lars-Ake Levin, Jessica Nordlund, Ulrika Noren-Nystrom, Josefine Palle, Tharshini Thangavelu, Lars Palmqvist, Valtteri Wirta, Lucia Cavelier, Thoas Fioretos, Richard Rosenquist, Clinical Genomics Platform SciLifeLab Genomic Med Sweden
Summary: This national multi-center study aims to evaluate the technical feasibility and efficiency of using whole-genome sequencing and whole-transcriptome sequencing as a diagnostic tool for patients with acute lymphoblastic leukemia and acute myeloid leukemia. The study comprises four phases and will involve approximately 700 patients, with endpoints including diagnostic efficiency, clinical feasibility, and health-economic impact.
FRONTIERS IN MEDICINE
(2022)
Article
Oncology
Cecilia Arthur, Fatemah Rezayee, Nina Mogensen, Leonie Saft, Richard Rosenquist, Magnus Nordenskjold, Arja Harila-Saari, Emma Tham, Gisela Barbany
Summary: This study demonstrates that whole-genome sequencing of genetic information in children with ALL, combined with ddPCR quantification, can accurately assess MRD levels. In addition, cfDNA extracted from plasma and cerebrospinal fluid can provide valuable information about MRD and low-grade CNS involvement.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Matthew Kaufman, Xiao-Jie Yan, Wentian Li, Emanuela M. Ghia, Anton W. Langerak, Laura Z. Rassenti, Chrysoula Belessi, Neil E. Kay, Frederic Davi, John C. Byrd, Sarka Pospisilova, Jennifer R. Brown, Mark Catherwood, Zadie Davis, David Oscier, Marco Montillo, Livio Trentin, Richard Rosenquist, Paolo Ghia, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Kostas Stamatopoulos, Thomas J. Kipps, Donna Neuberg, Nicholas Chiorazzi
Summary: Patients with mutated IGHV genes (M-CLL) have better outcomes, possibly due to suppressed BCR signaling that no longer delivers trophic signals to leukemic B cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Laurence de Leval, Ash A. Alizadeh, P. Leif Bergsagel, Elias Campo, Andrew Davies, Ahmet Dogan, Jude Fitzgibbon, Steven M. Horwitz, Ari M. Melnick, William G. Morice, Ryan D. Morin, Bertrand Nadel, Stefano A. Pileri, Richard Rosenquist, Davide Rossi, Itziar Salaverria, Christian Steidl, Steven P. Treon, Andrew D. Zelenetz, Ranjana H. Advani, Carl E. Allen, Stephen M. Ansell, Wing C. Chan, James R. Cook, Lucy B. Cook, Francesco D'Amore, Stefan Dirnhofer, Martin Dreyling, Kieron Dunleavy, Andrew L. Feldman, Falko Fend, Philippe Gaulard, Paolo Ghia, John G. Gribben, Olivier Hermine, Daniel J. Hodson, Eric D. Hsi, Giorgio Inghirami, Elaine S. Jaffe, Kennosuke Karube, Keisuke Kataoka, Wolfram Klapper, Won Seog Kim, Rebecca L. King, Young H. Ko, Ann S. LaCasce, Georg Lenz, Jose Martin-Subero, Miguel A. Piris, Stefania Pittaluga, Laura Pasqualucci, Leticia Quintanilla-Martinez, Scott J. Rodig, Andreas Rosenwald, Gilles A. Salles, Jesus San-Miguel, Kerry J. Savage, Laurie H. Sehn, Gianpietro Semenzato, Louis M. Staudt, Steven H. Swerdlow, Constantine S. Tam, Judith Trotman, Julie M. Vose, Oliver Weigert, Wyndham H. Wilson, Jane N. Winter, Catherine J. Wu, Pier L. Zinzani, Emanuele Zucca, Adam Bagg, David W. Scott
Summary: With the introduction of large-scale molecular profiling methods and high-throughput sequencing technologies, the genomic features of most lymphoid neoplasms have been characterized at an unprecedented scale. However, the current diagnosis of lymphoid tumors is largely based on morphological assessment and immunophenotyping, with only few entities being defined by genomic criteria. This paper discusses how established and newly developed molecular testing technologies complement clinical diagnoses and contribute to refining diagnosis, risk stratification, and therapy prediction for lymphoid neoplasms. Future methods such as whole-genome sequencing, circulating tumor DNA analyses, single-cell analyses, and epigenetic profiling are likely to become important tools for implementing precision medicine approaches in clinical decision making for lymphoid malignancies.
Letter
Biochemistry & Molecular Biology
Thoas Fioretos, Valtteri Wirta, Lucia Cavelier, Eva Berglund, Mikaela Friedman, Michael Akhras, Johan Botling, Hans Ehrencrona, Lars Engstrand, Gisela Helenius, Therese Fagerqvist, David Gisselsson, Sofia Gruvberger-Saal, Ulf Gyllensten, Markus Heidenblad, Kina Hoglund, Bo Jacobsson, Maria Johansson, Asa Johansson, Maria Johansson Soller, Marene Landstrom, Par Larsson, Lars-Ake Levin, Anna Lindstrand, Lovisa Lovmar, Anna Lyander, Malin Melin, Ann Nordgren, Gunnel Nordmark, Paula Molling, Lars Palmqvist, Richard Palmqvist, Dirk Repsilber, Per Sikora, Bianca Stenmark, Peter Soderkvist, Henrik Stranneheim, Tobias Strid, Craig E. Wheelock, Mia Wadelius, Anna Wedell, Anders Edsjo, Richard Rosenquist
Article
Oncology
Albrecht Stenzinger, Anders Edsjoe, Carolin Ploeger, Mikaela Friedman, Stefan Frohling, Valtteri Wirta, Thomas Seufferlein, Johan Botling, Justus Duyster, Michael Akhras, Robert Thimme, Thoas Fioretos, Michael Bitzer, Lucia Cavelier, Peter Schirmacher, Nisar Malek, Richard Rosenquist
Summary: In recent decades, advancements in technology and science have led to the integration of molecular sciences and clinical medicine, resulting in a better understanding of disease mechanisms and the development of novel therapies. Precision medicine, exemplified by precision oncology, holds great promise in various medical fields. Dedicated healthcare centers are required for the real-world implementation of precision medicine, gathering interdisciplinary expertise. Networks of such centers, like Genomic Medicine Sweden and the Centers for Personalized Medicine initiative in Germany, aim to provide a comprehensive framework for precision medicine. They seek to cover all aspects, from technology development to involvement of stakeholders, in order to ensure the sustainable and widespread implementation of precision medicine.
SEMINARS IN CANCER BIOLOGY
(2022)