Article
Hematology
W. Richard Burack, Hongli Li, Diana Adlowitz, Janice M. Spence, Lisa M. Rimsza, Mazyar Shadman, Catherine M. Spier, Mark S. Kaminski, John P. Leonard, Michael L. Leblanc, Sonali M. Smith, Jonathan W. Friedberg
Summary: Subclonal TP53 mutations are common in follicular lymphoma and are distinct from AICDA-mediated genetic heterogeneity. Patients with no detectable subclonal mutation in TP53 benefit particularly from RIT.
Article
Oncology
Nan Hu, Fangyang Wang, Tianyu Sun, Zhengfan Xu, Jing Zhang, Denzil Bernard, Shilin Xu, Shaomeng Wang, Mark Kaminski, Suma Devata, Tycel Phillips, Sami N. Malek
Summary: The study identified novel somatic BTK mutations in a small percentage of follicular lymphoma cases, demonstrating that these mutants destabilize the BTK protein and can induce an exaggerated AKT phosphorylation phenotype. The mutations did not affect PLC gamma 2 phosphorylation, but led to increased AKT phosphorylation following BCR cross-linking, with potential implications for targeted therapy development in follicular lymphoma.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Walter Hanel, Narendranath Epperla
Summary: Follicular Lymphoma (FL) is the most common subtype of indolent B cell non-Hodgkin lymphoma with heterogeneous clinical courses. Treatment options for FL include chemotherapy, immunotherapy, targeted therapy, and cellular therapy. Multiple combination therapies are currently in clinical trials, offering promising new treatment options for patients with FL.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Ruben Raychaudhuri, Chaitra Ujjani
Summary: The management of relapsed and refractory follicular lymphoma (FL) is challenging and ongoing investigation is being conducted. Recent studies have shown that epigenetic dysregulation is a characteristic of FL. Mutations in histone-modifying genes are likely to be early driver events in FL pathogenesis and are attractive drug targets. Mutations in the histone methyltransferase EZH2 are common in FL and are maintained throughout disease evolution. The small molecule inhibitor tazemetostat, developed based on the critical role of EZH2 as an oncogenic driver in FL, has shown promising activity in preclinical models and early phase trials. Importantly, it has shown responses in patients with high-risk features. Tazemetostat was approved in the US in 2020 for FL patients with EZH2 mutations who had received at least two prior lines of systemic therapy or for patients without alternative treatment options.
ONCOTARGETS AND THERAPY
(2022)
Article
Oncology
Alan Z. Skarbnik, Krish Patel
Summary: Follicular lymphoma (FL) is a common lymphoma with a variable clinical course. The response to treatment decreases with each line of therapy, and poor survival outcomes are associated with disease progression within 24 months of initial treatment. Although rituximab-based regimens are preferred for early lines of treatment, there is no clear standard of care for third-line treatment or later.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
C. Martinez-Laperche, L. Sanz-Villanueva, F. J. Diaz Crespo, P. Muniz, R. Martin Rojas, D. Carbonell, M. Chicano, J. Suarez-Gonzalez, J. Menarguez, M. Kwon, J. L. Diez Martin, I Buno, M. Bastos Oreiro
Summary: Mutations in EZH2 are found in nearly 25% of follicular lymphoma (FL) cases, but their impact on patients' response to therapy and outcomes is not well understood. This study retrospectively analyzed patients with FL to determine the frequency of EZH2 mutations at diagnosis in tissue and ctDNA and evaluated the patients' outcomes based on EZH2 mutation status. The results showed that mutated EZH2 was identified in both tissue samples and ctDNA, while patients without EZH2 mutations in tissue did not have mutations in ctDNA. Unmutated patients who received R-CHOP had a significantly higher relapse rate compared to those who received R-Bendamustine. Additionally, patients with mutated EZH2 treated with R-CHOP had a lower relapse rate, higher progression-free survival (PFS), and higher overall survival (OS) compared to those treated with R-Bendamustine. These findings suggest that EZH2 mutation status may serve as a useful biomarker for guiding upfront therapy in FL.
Review
Oncology
Danielle Wallace, Carla Casulo
Summary: Follicular lymphoma is an indolent lymphoma with most patients having normal life expectancy; however, approximately 20% of patients will experience disease progression within 24 months of diagnosis, leading to inferior survival outcomes. Recent studies have revealed novel prediction models and clinical trials utilizing novel therapies to identify and manage high-risk patients. Ongoing research efforts aim to improve management and survival outcomes for early progressing follicular lymphoma patients.
CURRENT ONCOLOGY REPORTS
(2021)
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
Biochemistry & Molecular Biology
Hui Si Kwok, Allyson M. Freedy, Allison P. Siegenfeld, Julia W. Morriss, Amanda L. Waterbury, Stephen M. Kissler, Brian B. Liau
Summary: Drug addiction in cancer cells reveals cell signaling mechanisms and dependencies. Mutations that confer drug addiction to inhibitors of the PRC2 transcriptional repressor are discovered in diffuse large B-cell lymphoma. Drug addiction is mediated by hypermorphic mutations in the CXC domain of the catalytic subunit EZH2, maintaining H3K27me3 levels even in the presence of inhibitors. Exploiting this vulnerability, inhibition of SETD2 induces the spread of H3K27me3 and blocks lymphoma growth. These findings demonstrate the role of chromatin landscapes in cancer cells and highlight the potential for discovering cancer vulnerabilities through drug addiction mutations.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Medicine, General & Internal
Akos Nagy, Bence Batai, Laura Kiss, Stefania Grof, Peter Attila Kiraly, Adam Jona, Judit Demeter, Hermina Santa, Arpad Batai, Piroska Pettendi, Tamas Szendrei, Mark Plander, Gabor Koeroesmezey, Hussain Alizadeh, Bela Kajtar, Gabor Mehes, Laszlo Krenacs, Botond Timar, Judit Csomor, Erika Toth, Tamas Schneider, Gabor Mikala, Andras Matolcsy, Donat Alpar, Andras Masszi, Csaba Bodor
Summary: A systematic analysis of EZH2 mutations in follicular lymphoma patients revealed a mutation frequency of 41.5%, higher than previously reported. This study expands the subset of patients who are likely to benefit from EZH2 inhibitor therapy.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Oncology
Michael Mentz, William Keay, Carolin Dorothea Strobl, Martina Antoniolli, Louisa Adolph, Michael Heide, Axel Lechner, Sarah Haebe, Elisa Osterode, Robert Kridel, Christoph Ziegenhain, Lucas Esteban Wange, Johannes Adrian Hildebrand, Tanaya Shree, Elisabeth Silkenstedt, Annette M. Staiger, German Ott, Heike Horn, Monika Szczepanowski, Julia Richter, Ronald Levy, Andreas Rosenwald, Wolfgang Enard, Ursula Zimber-Strobl, Michael Von Bergwelt-Baildon, Wolfgang Hiddemann, Wolfram Klapper, Marc Schmidt-Supprian, Martina Rudelius, Deepak Bararia, Verena Passerini, Oliver Weigert
Summary: The clinical course of follicular lymphoma (FL) is influenced by the molecular heterogeneity of tumor cells and interactions within the tumor microenvironment (TME). In this study, we found STAT6 mutations in 13% of FL cases, which enhanced the response of FL cells to IL-4 and were associated with increased expression of target genes and nuclear accumulation of pSTAT6. We identified PARP14 as a potential therapeutic target in STAT6-mutated FL cells, as its expression was upregulated and it played a role in the regulatory circuit.
Editorial Material
Hematology
Robin Gasiorowski, Judith Trotman
Summary: In this study, the effectiveness of axicabtagene ciloleucel in treating patients with multiply relapsed follicular lymphoma was compared. The results showed that axicabtagene ciloleucel had excellent efficacy, with prolonged progression-free survival and significantly improved overall survival.
Article
Multidisciplinary Sciences
Isabel Gomez-Reldondo, Eva Pericuesta, Paula Navarrete-Lopez, Priscila Ramos-Ibeas, Benjamin Planells, Noelia Fonseca-Balvis, Aida Vaquero-Rey, Raul Fernandez-Gonzalez, Ricardo Laguna-Barraza, Keiko Horiuchi, Alfonso Gutierrez-Adan
Summary: ZRSR2 mutations affect blood cell, oogenesis, and female fertility by altering gene expression and alternative splicing events, mainly in U12-type introns.
Article
Oncology
Joseph G. Schroers-Martin, Joanne Soo, Gabriel Brisou, Florian Scherer, David M. Kurtz, Brian J. Sworder, Michael S. Khodadoust, Michael C. Jin, Agnes Bru, Chih Long Liu, Henning Stehr, Paolo Vineis, Yasodha Natkunam, Lauren R. Teras, Joo Y. Song, Bertrand Nadel, Maximilian Diehn, Sandrine Roulland, Ash A. Alizadeh
Summary: Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. CREBBP KAT domain mutations were the most commonly observed precursor lesions, distinguishing patients developing FL from healthy adults with or without BCL2 rearrangements. These mutations can be detected years before clinical diagnosis and may help discriminate individuals at risk for lymphoma development.
Article
Oncology
Ismael Fernandez-Miranda, Lucia Pedrosa, Marta Llanos, Fernando F. Franco, Sagrario Gomez, Paloma Martin-Acosta, Francisco R. Garcia-Arroyo, Josep Guma, Beatriz Horcajo, Ana K. Ballesteros, Laura Galvez, Natividad Martinez, Miguel Marin, Silvia Sequero, Marta Navarro, Natalia Yanguas-Casas, Virginia Calvo, Antonio Rueda-Dominguez, Mariano Provencio, Margarita Sanchez-Beato
Summary: This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and early disease progression in follicular lymphoma (FL) patients. The results showed that baseline ctDNA levels are associated with early disease progression and treatment response in FL.
CLINICAL CANCER RESEARCH
(2023)
Letter
Hematology
Richard Dillon, Robert K. Hills, Alan K. Burnett, Nigel H. Russell
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
David C. Linch, Robert K. Hills, Alan K. Burnett, Nigel Russell, Rosemary E. Gale
Summary: The study found an improved outcome for younger adult patients with IDH2(R172)-mutated acute myeloid leukaemia in later trials, attributed to the increased use of allogeneic transplantation for consolidating first remission.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Editorial Material
Hematology
Robert K. Hills
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Nigel Russell, Robert Hills, Lars Kjeldsen, Mike Dennis, Alan Burnett
Summary: For younger patients with secondary AML, treatment intensification with FLAG-Ida may lead to superior 5-year overall survival and relapse free survival compared to traditional DA/ADE regimens, suggesting that 3 + 7 chemotherapy may not be the optimal comparator for this group of patients in clinical trials.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Letter
Hematology
Robert K. Hills
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Letter
Oncology
Hannah Armes, Ana Rio-Machin, Szilvia Krizsan, Csaba Bodor, Fadimana Kaya, Findlay Bewicke-Copley, Jenna Alnajar, Amanda Walne, Borbala Peterffy, Hemanth Tummala, Kevin Rouault-Pierre, Inderjeet Dokal, Tom Vulliamy, Jude Fitzgibbon
Review
Hematology
Lili Kotmayer, Damia Romero-Moya, Oskar Marin-Bejar, Emilia Kozyra, Albert Catala, Anna Bigas, Marcin W. Wlodarski, Csaba Bodor, Alessandra Giorgetti
Summary: The importance of predisposition to leukemia, especially GATA2 deficiency, with a high risk of developing myelodysplastic syndrome and acute myeloid leukemia, is increasingly recognized. Allogenic hematopoietic stem cell transplantation is the only curative option, but chances of survival decrease with progression of immunodeficiency and disease evolution. Variability in penetrance and expressivity within families carrying GATA2 mutations suggests the involvement of cooperating extrinsic events in triggering the disease. Lack of predictive tools and understanding of intrafamilial heterogeneity highlights the need for further research in this area.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Orsolya Juhasz, Noemi Jakob, Hajnalka Rajnai, Marcell Imrei, Miklos Garami
Summary: The study found that lower vitamin D receptor (VDR) expression is associated with worse prognosis in different types of childhood cancer. Identifying the VDR status provides clinicians with a valuable biomarker to guide additional therapy.
Correction
Pathology
Birgitta Sander, Elias Campo, Eric D. Hsi
Review
Pathology
Birgitta Sander, Elias Campo, Eric D. Hsi
Summary: This manuscript reviews the clinicopathologic and biologic features of chronic lymphocytic leukaemia/small lymphocytic lymphoma, B-cell prolymphocytic leukaemia, and mantle cell lymphoma. Discussions focus on incorporating new knowledge into the next classification system.
Editorial Material
Hematology
Robert K. Hills
Summary: Prolonged cytopaenia is a recognized issue after CAR-T cell therapy, but the causes and implications are still unknown. Kitamura et al.'s study identified that alterations in the bone marrow niche prior to CAR-T therapy may be a potential predictor for long-term cytopaenia, shedding light on this serious side-effect of treatment.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Robert K. Hills
Summary: The paper by Noor et al. presents significant findings on the incidence and outcomes of patients with acute myeloid leukaemia in Afghanistan. It highlights the lower age of patients compared to the Western standard, reflecting the unique demographics of the country. These findings serve as an important initial step in identifying areas for improvement.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Surgery
Timea Teszak, Csaba Bodor, Lajos Hegyi, Luca Levay, Beata Nagy, Attila Fintha, Bela Merkely, Balazs Sax
Summary: This study reports the first 6 months of experience with a local laboratory-run dd-cfDNA assay in the routine clinical surveillance setting. The results show that most patients had continuously low dd-cfDNA fractions, allowing safe avoidance of the majority of surveillance endomyocardial biopsies (EMBs). EMBs were only performed when the dd-cfDNA fraction was ≥0.25%, and there were no missed rejections.
CLINICAL TRANSPLANTATION
(2023)
Article
Hematology
Mhairi Copland, Cono Ariti, Ian F. Thomas, Laura Upton, Mia Sydenham, Priyanka Mehta, Shahid Islam, Lars Kjeldsen, Alan K. Burnett, Robert K. Hills, Nigel Russell, Mike Dennis
Summary: Improving outcomes for older patients with acute myeloid leukaemia is still an unmet need. In this study, we evaluated the effectiveness of lenalidomide in combination with low-dose cytosine arabinoside compared to low-dose cytosine arabinoside alone in unfit patients aged over 60. The combination therapy showed a higher overall response rate, but there was no difference in overall survival between the two arms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gergely Buki, Anna Beko, Csaba Bodor, Peter Urban, Krisztina Nemeth, Kinga Hadzsiev, Gyoergy Fekete, Hildegard Kehrer-Sawatzki, Judit Bene
Summary: Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder with a portion of cases caused by microdeletions of the NF1 gene. These microdeletions lead to more severe clinical manifestations and often exhibit specific additional clinical symptoms. Identifying the co-deleted genes is crucial for understanding the pathogenesis and clinical manifestations of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
