Review
Hematology
Emil Kumar, Lucy Pickard, Jessica Okosun
Summary: Follicular lymphoma (FL) is a heterogeneous disease with increasing recognition of recurrent genetic alterations in epigenetic regulators as a pivotal hallmark. Studies are beginning to uncover the convergence between genetics, epigenetics, and the tumor microenvironment, emphasizing the need to integrate biology with therapeutics for optimal patient care.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Editorial Material
Immunology
Krystal S. A. Lianos, Anne L. Fletcher
Summary: Fibroblasts play a crucial role in shaping the immune landscape of lymph nodes, and understanding their interactions with T and B cells could uncover potential clinical targets in follicular lymphoma.
Article
Oncology
Sabrina Kalmbach, Michael Grau, Myroslav Zapukhlyak, Ellen Leich, Vindi Jurinovic, Eva M. Hoster, Annette S. Staiger, Katrin Kurz, Oliver Weigert, Erik Gaitzsch, Verena Passerini, Marianne Engelhard, Klaus Herfarth, Klaus Beiske, Francesca Micci, Peter Moeller, Heinz-Wolfram C. Bernd, Alfred Feller, Wolfram Klapper, Harald Stein, Martin-Leo Hansmann, Sylvia Hartmann, Martin Dreyling, Harald Holte, Georg Lenz, Andreas Rosenwald, German Ott, Heike Horn, German Lymphoma Alliance GLA
Summary: Comprehensive analysis of localized follicular lymphoma (lFL) and systemic follicular lymphoma (sFL) revealed overlapping genetic and chromosomal abnormalities. However, significant differences were found in the frequency of chromosomal alterations, specifically in 18q gains. Rare gains in 18q21 were associated with inferior progression-free survival in lFL. ARID1A mutations were more frequently detected in sFL compared to lFL. This study provides novel insights and identifies 18q21 gains as a prognostic marker in lFL.
Article
Pathology
Yuka Takahashi, Hirokazu Taniguchi, Furukawa Haruhi, Daiki Hattori, Hirokazu Sasaki, Shinichi Makita, Noriko Iwaki, Suguru Fukuhara, Wataru Munakata, Yutaka Saito, Koji Izutsu, Akiko M. Maeshima
Summary: Gastrointestinal follicular lymphoma can occur in the small intestine, stomach, and colon, with the small intestine being the most common site. There are differences in endoscopic and histopathologic findings among different sites, which may be attributed to variations in mucosal structure and the size of neoplastic follicles.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Review
Health Care Sciences & Services
Karthik Nath, Maher K. Gandhi
Summary: Follicular lymphoma, the most common indolent B-cell lymphoma, has different prognoses, but the emergence of novel targeted agents offers hope for future treatment options.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Oncology
Jonathan W. Friedberg
Summary: Remarkable progress has been made in understanding and treating follicular lymphoma in the past two decades. Long-term follow-up studies have shown that up to 40% of patients can achieve remission durations of 10 or more years, and the risk of dying from lymphoma continues to decrease. Recent advancements in staging, prognosis, and immunotherapy have further improved treatment options. Ongoing trials will help determine the optimal sequence of treatments, potentially leading to a cure for this disease. Precision management of follicular lymphoma is becoming a realistic goal through continued research and studies.
HEMATOLOGICAL ONCOLOGY
(2023)
Review
Oncology
Rada Amin, Mounia S. Braza
Summary: This review provides a detailed description of the impact of epigenomic alterations on the immune microenvironment in follicular lymphoma (FL) and discusses the latest progress in targeting epigenetic pathways to inhibit the FL microenvironment. The article highlights unexplored research areas and key questions that need to be addressed.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Oncology
James A. Fagin, Gnana P. Krishnamoorthy, Inigo Landa
Summary: This review outlines the genomic simplicity of differentiated cancers derived from thyroid follicular cells and explores the impact of oncogenic drivers on tumor phenotypes. The activation of key nodes in the receptor tyrosine kinase-RAS-BRAF pathway by oncoproteins in thyroid cancer leads to constitutive MAPK signaling with varying degrees of activity based on their specific biochemical mechanisms. The magnitude of MAPK signaling determines important aspects of thyroid cancer biology, including differentiation state, invasiveness, and tumor microenvironment. Genomic lesions, chromatin accessibility disruption, cell cycle dysfunction, and progressive immunosuppression in the tumor microenvironment contribute to disease progression.
NATURE REVIEWS CANCER
(2023)
Article
Oncology
Yanan Li, Yan Zhang, Wei Wang, Chong Wei, Danqing Zhao, Wei Zhang
Summary: This study aims to evaluate prognostic predictors of follicular lymphoma among Chinese patients. The study found that LMR is a new independent predictor that has better predictive ability compared to FLIPI.
CANCER MANAGEMENT AND RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Tianyuan Xu, Zhong Zheng, Weili Zhao
Summary: Follicular lymphoma (FL) is a heterogeneous lymphoma originating from germinal center B cells. Multi-omics analysis has revealed abnormalities in FL cells and tumor microenvironment, providing insights into the mechanisms of FL progression and potential therapeutic options.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Editorial Material
Hematology
James D. Phelan, Elaine S. Jaffe
Summary: In this study, the authors used whole genome sequencing to investigate the basis of follicular lymphoma (FL) transformation. They identified two genetically distinct subgroups of FL, dFL and cFL, which showed a significant difference in time to transformation.
Article
Hematology
Eric Jacobsen
Summary: Follicular lymphoma is a slow-growing B cell lymphoproliferative disorder characterized by lymph node enlargement, bone marrow involvement, and spleen enlargement. Diagnosis is usually made through histological examination of affected lymph nodes or other tissues. The Follicular Lymphoma International Prognostic Index (FLIPI) is a useful tool for risk stratification and predicting patient outcomes.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Medicine, General & Internal
Shahed Azzam Ahmed Abdullah, Patricia Goa, Elisabeth Vandenberghe, Richard Flavin
Summary: EATL is an aggressive T-cell lymphoma primarily affecting the small intestine, with a close association with coeliac disease (CD). Various factors, including viral infection, advanced age, male gender, and HLA-DQ2 haplotype, increase the risk of developing EATL. Clonal rearrangements in TCR-beta and gamma genes are observed in all morphological variants of EATL, which have distinctive immunophenotypic characteristics. Recent evidence suggests that EATL may originate from small intestinal intraepithelial T-lymphocytes (IELs) or innate precursor IELs in refractory coeliac disease type II (RCDII). The immune microenvironment and dysregulation of the JAK-STAT signaling pathway play important roles in the neoplastic transformation of IELs into EATL, with cytokines like IL-15 and mutations in the JAK/STAT pathway being implicated in RCDII-derived EATL.
Editorial Material
Hematology
Connie Lee Batlevi
Summary: The tolerability and efficacy of obinutuzumab and lenalidomide in frontline therapy of follicular lymphoma are reported in this study.
Review
Pharmacology & Pharmacy
Michael Northend, William Townsend
Summary: Follicular lymphoma is the most common form of indolent non-Hodgkin lymphoma, with a long median overall survival and high response rates to current therapies. Some patients show aggressive behavior or resistance to treatment, leading to poor outcomes, but new therapies like lenalidomide and immunotherapies are offering hope for the future.
Review
Oncology
Marc A. Weniger, Ralf Kuppers
Summary: Classical Hodgkin lymphoma (cHL) has unique biological features such as the orchestration of a complex microenvironment by HRS cells, the major role of Epstein-Barr virus in lymphomagenesis, and the defining interplay of genetic lesions and cellular origin. These factors contribute to the constitutive activation of multiple signaling pathways in cHL.
Editorial Material
Biotechnology & Applied Microbiology
Yingying Cao, Simo Kitanovski, Ralf Kueppers, Daniel Hoffmann
NATURE BIOTECHNOLOGY
(2021)
Editorial Material
Immunology
Ralf Kueppers
Summary: The generation and function of B lymphocytes are well explained in the publications of JEM, focusing on landmark studies on normal B cell immunology.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Hematology
Giorgia Chiodin, Joel D. Allen, Dean J. Bryant, Philip Rock, Enrica A. Martino, Beatriz Valle-Argos, Patrick J. Duriez, Yasunori Watanabe, Isla Henderson, James S. Blachly, Katy J. McCann, Jonathan C. Strefford, Graham Packham, Teunis B. H. Geijtenbeek, Carl G. Figdor, George W. Wright, Louis M. Staudt, Richard Burack, Thomas A. Bowden, Max Crispin, Freda K. Stevenson, Francesco Forconi
Summary: The glycosylation of the Ig variable region is a rare feature associated with follicular lymphoma, and some DLBCLs acquire N-glycosylation sites selectively in the CDRs of the antigen-binding sites, particularly in the EZB subtype; this contrasts with the activated B-cell-like DLBCL Ig. The acquisition of these sites is associated with mutations of epigenetic regulators and BCL2 translocations, and the oligomannosylated tumor Ig can be a potential therapeutic target against DC-SIGN-expressing M2-polarized macrophages.
Editorial Material
Hematology
Ralf Kueppers
Summary: Transcription factors OBF1, OCT1, and OCT2 are essential for the germinal center B-cell program in a murine model, directly regulating key factors involved in GC B-cell development and maintaining proliferation of several types of B-cell lymphoma cell lines.
Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Multidisciplinary Sciences
Beatriz Valle-Argos, Giorgia Chiodin, Dean J. Bryant, Joe Taylor, Elizabeth Lemm, Patrick J. Duriez, Philip J. Rock, Jonathan C. Strefford, Francesco Forconi, Richard W. Burack, Graham Packham, Freda K. Stevenson
Summary: In follicular lymphoma, lectin DC-SIGN modulates the function of sIg by binding to acquired mannoses, triggering cell signaling pathways similar to anti-IgM, activating pathways associated with B-cell survival, proliferation and cell-cell communication. This alternative engagement of the B-cell receptor provides lymphoma cells with activation of signaling responses and protection from exogenous antigens.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Hematology
Ralf Kueppers
Summary: The study shows that a specific subgroup of DLBCLs frequently acquire N-glycosylation sites in their BCR genes, carrying oligomannose-type glycans that promote BCR signaling, most likely by binding to lectins in the lymphoma microenvironment.
Review
Oncology
Manuel Montesinos-Rongen, Anna Brunn, Monica Sanchez-Ruiz, Ralf Kueppers, Reiner Siebert, Martina Deckert
Summary: The pathogenesis of primary CNS lymphoma (PCNSL) involves a failure in B cell differentiation and a lack of control during the entrance and within the germinal center (GC) stages. Targeted molecular studies have shown that activated pathways promote lymphoma cell proliferation, leading to tumor cells being trapped in a late B cell differentiation stage. This may contribute to the increased affinity of the lymphoma for the CNS.
Article
Oncology
Patricia Johansson, Anja Eckstein, Ralf Kueppers
Summary: Ocular adnexal marginal zone lymphoma (OAMZL) is a distinct type of lymphoma that occurs in tissues around the eyeball. The development of this lymphoma is associated with the constitutive activation of the NF-kappa B pathway, which may be caused by genetic alterations and epigenetic changes. The mucosa-associated lymphatic tissue (MALT) subtype is the most common subtype of lymphoma in the ocular adnexa.
Article
Hematology
Giorgia Chiodin, Samantha Drennan, Enrica A. Martino, Laura Ondrisova, Isla Henderson, Luis del Rio, Ian Tracy, Annalisa D'Avola, Helen Parker, Silvia Bonfiglio, Lydia Scarfo, Lesley-Ann Sutton, Jonathan C. Strefford, Jade Forster, Oliver Brake, Kathleen N. Potter, Benjamin Sale, Stuart Lanham, Marek Mraz, Paolo Ghia, Freda K. Stevenson, Francesco Forconi
Summary: Chronic lymphocytic leukemia (CLL) cells with high surface IgM (sIgM) levels progress more rapidly and can regain sIgM expression during ibrutinib therapy. High sIgM levels are associated with shorter time to new treatment. Ibrutinib inhibits sIgM-mediated signaling more effectively in CLL cells with low sIgM levels.
Article
Cell Biology
Rachael Arthur, Alexander Wathen, A. Elizabeth Lemm, K. Freda Stevenson, Francesco Forconi, J. Adam Linley, J. Andrew Steele, Graham Packham, Beatriz Valle-Argos
Summary: BTK inhibitors (BTKi) have shown significant improvement in the treatment of chronic lymphocytic leukemia (CLL) and certain forms of B-cell lymphoma. However, the activation of BTK-independent calcium signaling may limit the efficacy of BTKi. Inhibition of SYK or dual inhibition of BTK and RAC may be alternative strategies to enhance pathway blockade.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Barbara Uhl, Katharina T. Prochazka, Katrin Pansy, Kerstin Wenzl, Johanna Strobl, Claudia Baumgartner, Marta M. Szmyra, James E. Waha, Axel Wolf, Peter Tomazic, Elisabeth Steinbauer, Maria Steinwender, Sabine Friedl, Marc Weniger, Ralf Kueppers, Martin Pichler, Hildegard T. Greinix, Georg Stary, Alan G. Ramsay, Benedetta Apollonio, Julia Feichtinger, Christine Beham-Schmid, Peter Neumeister, Alexander J. Deutsch
Summary: Chemokine receptors and their ligands play an important role in the development of DLBCL, follicular lymphoma, and RS. This study found that the expression profiles of chemokine receptors in de novo DLBCL and tFL were significantly different from that of GC-B and RS. High expression of CCR7 was associated with poor overall survival in patients with de novo DLBCL and tFL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Dean Bryant, Lindsay Smith, Karly Rai Rogers-Broadway, Laura Karydis, Jeongmin Woo, Matthew D. Blunt, Francesco Forconi, Freda K. Stevenson, Christopher Goodnow, Amanda Russell, Peter Humburg, Graham Packham, Andrew J. Steele, Jonathan C. Strefford
Summary: Chronic lymphocytic leukaemia (CLL) cells can express unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain (IGHV) genes, with differences in clinical behaviors, B cell receptor (BCR) signaling capacity, and transcriptional profiles. Through mRNA/miRNA sequencing of 38 CLL cases, researchers identified differentially expressed mRNAs and miRNAs between U-CLL and M-CLL, as well as potential regulatory roles of the 14q32 miRNA locus in CLL-related gene regulation and BCR signaling.
Editorial Material
Hematology
Ralf Kueppers
Summary: In this study, the authors demonstrate that inhibiting mRNA translation with flavagline FL3 has multiple effects on CLL cells, including blocking proliferation, rewiring MYC-driven metabolism, and controlling CLL growth in a murine model.