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Articles by Robert Kridel
Detection and classification of lymphoma from cell-free methylome data
Abstract Diagnosing lymphoma traditionally relies on invasive tissue biopsies, which can yield insufficient material for histopathological evaluation and carry a risk of complications. Minimally invasive assessment of cell-free DNA (cfDNA) in plasma offers a promising alternative for lymphoma detection that could aid the rapid evaluation of malignant vs. benign lymphadenopathy.
Blood-based epigenetic instability linked to human aging and disease - Nature Communications
Abstract The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception.
Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Simulating cell-free chromatin using preclinical models for cancer-specific biomarker discovery
Abstract Cell-free chromatin (cf-chromatin) is a rich source of biomarkers across various conditions, including cancer. Tumor-derived circulating cf-chromatin can be profiled for epigenetic features, including nucleosome positioning and histone modifications that govern cell type-specific chromatin conformations. However, the low fractional abundance of tumor-derived cf-chromatin in blood and constrained access to plasma samples pose challenges for epigenetic biomarker discovery.
PARP14 is a novel target in STAT6 mutant follicular lymphoma - Leukemia
Abstract The variable clinical course of follicular lymphoma (FL) is determined by the molecular heterogeneity of tumor cells and complex interactions within the tumor microenvironment (TME). IL-4 producing follicular helper T cells (TFH) are critical components of the FL TME. Binding of IL-4 to IL-4R on FL cells activates JAK/STAT signaling. We identified STAT6 mutations (STAT6MUT) in 13% of FL (N = 33/258), all clustered within the DNA binding domain.
Treatment resistance in diffuse large B-cell lymphoma
References 1. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. Cancer J Clin. 2016;66:443–59. Article Google Scholar 2. Ennishi D, Hsi ED, Steidl C, Scott DW. Toward a new molecular taxonomy of diffuse large B-cell lymphoma. Cancer Discov. 2020;10:1267–81. CAS PubMed Article PubMed Central Google Scholar 3. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al.
TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma
Abstract Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and ‘eat-me’ signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL.
Early progression after bendamustine-rituximab is associated with high risk of transformation in advanced stage follicular lymphoma
Ciara L. Freeman, Robert Kridel, Alden A. Moccia, Kerry J. Savage, Diego R. Villa, David W. Scott, Alina S. Gerrie, David Ferguson, Fergus Cafferty, Graham W. Slack, Pedro Farinha, Brian Skinnider, Joseph M. Connors and Laurie H. Sehn Blood 2019 134:761-764; doi: https://doi.org/10.1182/blood.2019000258 Key Points Frontline bendamustine and rituximab in advanced stage FL has marked efficacy in this population-based analysis.
Rituximab as a first step in tackling transformation
The earliest description of follicular lymphoma transformation dates back to the 1940s, when a sequential biopsy from a patient was identified to have a “less differentiated appearance”.More than 70 years on, we still do not have a uniform definition of transformation, with the widely accepted dogma of confirmation through a repeat biopsy not followed universally for wide-ranging reasons.
Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland
Solid organ transplant recipients have an elevated cancer risk due to immunosuppression and subsequent oncogenic viral infections [1]. Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication in up to 20% of transplanted patients [2], with non-Hodgkin’s lymphoma accounting for 93% of cases [3].
Novel insights into the disease dynamics of B‐cell lymphomas in the Genomics Era
High‐throughput sequencing has significantly contributed to revealing the molecular underpinnings of B‐cell lymphomagenesis and disease progression. It is now a widely accepted concept that the diversity of clinical responses to front‐line therapy and the development of relapsed/refractory disease are in part explained by ‘inter‐patient’ genetic heterogeneity measurable by individual sets of somatic gene alterations in tumor genomes.
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