Publications
403 results found
Bewicke-Copley F, Korfi K, Araf S, et al., 2023, Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma., Blood Adv, Vol: 7, Pages: 845-855
Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell-like (ABC) to germinal center B-cell-like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.
Pai SA, Naresh KN, Borges AM, 2022, Report of a Case With Clinical and Pathologic Features of Castleman Disease That Predates Castleman's Report by More Than 50 Years., Arch Pathol Lab Med, Vol: 146, Pages: 1412-1415
CONTEXT.—: In 1954, Benjamin Castleman, MD, described what was then believed to be a new entity in lymph node pathology. Initially labeled "Hyperplasia of the mediastinal node" and then "Localized mediastinal lymph node hyperplasia resembling thymoma," we now recognize the condition with the eponym "Castleman disease." We document a paper that describes the same condition, a half century before Castleman did. OBJECTIVE.—: To report the striking resemblance between Castleman disease and the lymph node reported in the paper published by Edwin R. LeCount, MD, titled "Lymphoma, a benign tumor representing a lymph gland in structure," published in Journal of Experimental Medicine in 1899. We also provide an overview of the remarkable achievements of LeCount. DESIGN.—: We compared the elucidation in the original paper by LeCount with the morphologic details in the papers published by Castleman et al. Material on the life of LeCount was compiled from the scientific literature, the Internet, and the files of the University of Chicago. RESULTS.—: LeCount's description and illustrations of the lymph node are uncannily similar to the onion-skinning and vascularity that Castleman documented. CONCLUSIONS.—: LeCount deserves credit for his depiction of a hitherto-unreported entity.
Naresh KN, 2022, Proposal of 'reactive-lymphocyte/histiocyte rich large B-cell lymphoma' as an alternate term for 'nodular lymphocyte predominant Hodgkin lymphoma' that would also address its overlap with T-cell/histiocyte rich large B-cell lymphoma., EJHaem, Vol: 3, Pages: 1449-1451
Fromm JR, Tang C, Naresh KN, 2022, Predictors of risk of relapse in classic Hodgkin lymphoma, JOURNAL OF CLINICAL PATHOLOGY, ISSN: 0021-9746
Ju JY, Sorensen EP, Walsh JS, et al., 2022, CD5(+) Gamma Delta T-Cell Lymphoproliferative Disorder/Lymphoma Without Cytotoxic Granules in the Skin, AMERICAN JOURNAL OF DERMATOPATHOLOGY, Vol: 44, Pages: 680-682, ISSN: 0193-1091
Naik A, Gooley T, Loeb K, et al., 2022, The impact of histological grade on outcomes in follicular lymphoma: An analysis of patients in the SEER database in the context of evolving disease classification and treatment, BRITISH JOURNAL OF HAEMATOLOGY, Vol: 199, Pages: 696-706, ISSN: 0007-1048
Khoury JD, Solary E, Abla O, et al., 2022, The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms, LEUKEMIA, Vol: 36, Pages: 1703-1719, ISSN: 0887-6924
- Author Web Link
- Cite
- Citations: 185
Alaggio R, Amador C, Anagnostopoulos I, et al., 2022, The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms, Leukemia, Vol: 36, Pages: 1720-1748, ISSN: 0887-6924
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
Stacey A, Marks AJ, Naresh KN, 2022, Variant histology in nodular lymphocyte predominant Hodgkin lymphoma in an adult population: disease investigations and characteristics from a retrospective cohort, JOURNAL OF CLINICAL PATHOLOGY, Vol: 76, Pages: 137-140, ISSN: 0021-9746
- Author Web Link
- Cite
- Citations: 1
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2022, Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma, BLOOD, Vol: 139, Pages: 1939-1953, ISSN: 0006-4971
- Author Web Link
- Cite
- Citations: 6
Ponnusamy K, Tzioni MM, Begum M, et al., 2022, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma, HAEMATOLOGICA, Vol: 107, Pages: 721-732, ISSN: 0390-6078
- Author Web Link
- Cite
- Citations: 5
Attygalle AD, Dobson R, Chak PK, et al., 2022, Parallel evolution of two distinct lymphoid proliferations in clonal haematopoiesis, HISTOPATHOLOGY, Vol: 80, Pages: 847-858, ISSN: 0309-0167
- Author Web Link
- Cite
- Citations: 3
Ibanez K, Polke J, Hagelstrom RT, et al., 2022, Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study, LANCET NEUROLOGY, Vol: 21, Pages: 234-245, ISSN: 1474-4422
- Author Web Link
- Cite
- Citations: 14
Chen X, Fromm JR, Naresh KN, 2022, "Blasts" in myeloid neoplasms - how do we define blasts and how do we incorporate them into diagnostic schema moving forward?, LEUKEMIA, Vol: 36, Pages: 327-332, ISSN: 0887-6924
- Author Web Link
- Cite
- Citations: 2
Naresh KN, Lazzi S, Santi R, et al., 2021, A refined approach to the diagnosis of Burkitt lymphoma in a resource-poor setting, HISTOPATHOLOGY, Vol: 80, Pages: 743-745, ISSN: 0309-0167
- Author Web Link
- Cite
- Citations: 2
Trasanidis N, Katsarou A, Ponnusamy K, et al., 2021, Systems medicine dissection of chromosome 1q amplification reveals oncogenic regulatory circuits and informs targeted therapy in cancer
<jats:title>Abstract</jats:title><jats:p>Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.</jats:p><jats:sec><jats:title>Significance</jats:title><jats:p>We provide a comprehensive systems medicine strategy to unveil oncogenic circuitries and inform novel precision therapy decisions against CNA in cancer. This first clinical multi-omic analysis of chr1q-amp in MM identifies a central PBX1-FOXM1 regulatory axis driving high-risk prognosis, as a novel therapeutic target against chr1q-amp in cancer.</jats:p></jats:sec>
Smedley D, Smith KR, Martin A, et al., 2021, 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 1868-1880, ISSN: 0028-4793
- Author Web Link
- Cite
- Citations: 102
Medani H, Elshiekh M, Naresh KN, 2021, Improving precise counting of mitotic cells in mantle cell lymphoma using phosphohistone H3 (PHH3) antibody, JOURNAL OF CLINICAL PATHOLOGY, Vol: 74, Pages: 646-649, ISSN: 0021-9746
Claudiani S, Mason CC, Milojkovic D, et al., 2021, Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis, CANCERS, Vol: 13
Xu D, Naresh KN, 2021, Leukemic presentation of a highly aggressive ALK-negative anaplastic large cell lymphoma, BLOOD, Vol: 138, Pages: 1198-1198, ISSN: 0006-4971
Iskander D, Wang G, Heuston EF, et al., 2021, Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234
- Author Web Link
- Cite
- Citations: 9
Ibanez K, Polke J, Hagelstrom T, et al., 2020, Whole genome sequencing for diagnosis of neurological repeat expansion disorders
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Repeat expansion (RE) disorders affect ~1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in under diagnosis of atypical clinical presentations, especially in paediatric patients without a prior positive family history. Whole genome sequencing (WGS) is emerging as a first-line test for rare genetic disorders, but until recently REs were thought to be undetectable by this approach.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>WGS pipelines for RE disorder detection were deployed by the 100,000 Genomes Project and Illumina Clinical Services Laboratory. Performance was retrospectively assessed across the 13 most common neurological RE loci using 793 samples with prior orthogonal testing (182 with expanded alleles and 611 with alleles within normal size) and prospectively interrogated in 13,331 patients with suspected genetic neurological disorders.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>WGS RE detection showed minimum 97·3% sensitivity and 99·6% specificity across all 13 disease-associated loci. Applying the pipeline to patients from the 100,000 Genomes Project identified pathogenic repeat expansions which were confirmed in 69 patients, including seven paediatric patients with no reported family history of RE disorders, with a 0.09% false positive rate.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>We show here for the first time that WGS enables the detection of causative repeat expansions with high sensitivity and specificity, and that it can be used to resolve previously undiagnosed neurological disorders. This includes children w
Iskander D, Wang G, Heuston EF, et al., 2020, Single-Cell Transcriptional Landscapes of Human Bone Marrow Reveal Distinct Erythroid Phenotypes Underpinned By Genotype in Diamond-Blackfan Anemia, 62nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Ziepert M, Lazzi S, Santi R, et al., 2020, A 70% cut-off for MYC protein expression in diffuse large B-cell lymphoma identifies a high-risk group of patients, HAEMATOLOGICA, Vol: 105, Pages: 2667-2670, ISSN: 0390-6078
- Author Web Link
- Cite
- Citations: 10
Ziepert M, Lazzi S, Santi R, et al., 2020, A 70% cut-off for MYC protein expression in diffuse large B cell lymphoma identifies a high-risk group of patients., Haematologica, Vol: 105, Pages: 2667-2670
Hanley B, Naresh KN, Roufosse C, et al., 2020, Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study, The Lancet Microbe, Vol: 1, Pages: e245-e253, ISSN: 2666-5247
BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of
Thomas SJ, Morley N, Lashen H, et al., 2020, Indolent T-Cell Lymphoproliferative Disorder of the Uterine Corpus: A Case Report, INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY, Vol: 39, Pages: 503-506, ISSN: 0277-1691
- Author Web Link
- Cite
- Citations: 1
Ponnusamy K, Tzioni MM, Begum M, et al., 2020, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma
<jats:title>Abstract</jats:title><jats:p>ZBP1 is an inducible, non-constitutively expressed cellular nucleic acid sensor that triggers type I interferon (IFN) responses via phosphorylation and activation of the transcription factor (TF) IRF3 by TBK1. However, the role of the ZBP1-IRF3 axis in cancer is not known. Here we show that ZBP1 is selectively and constitutively expressed in late B cell development and it is required for optimal T cell-dependent humoral immune responses. In the plasma cell (PC) cancer multiple myeloma, interaction of constitutively expressed ZBP1 with TBK1 and IRF3 results in IRF3 phosphorylation. Notably, rather than IFN type I response genes, IRF3 directly activates, in part through co-operation with the PC lineage-defining TF IRF4, cell cycle genes thus promoting myeloma cell proliferation. This generates a novel, potentially therapeutically targetable and relatively selective myeloma cell addiction to the ZBP1-IRF3 axis. These data expand our knowledge of the role of cellular immune sensors in cancer biology.</jats:p>
Hanley B, Roufosse CA, Osborn M, et al., 2020, Convalescent donor SARS-COV-2-specific cytotoxic T lymphocyte infusion as a possible treatment option for COVID-19 patients with severe disease has not received enough attention till date., British Journal of Haematology, Vol: 189, Pages: 1062-1063, ISSN: 0007-1048
Shah V, Sherborne AL, Johnson DC, et al., 2020, Predicting ultrahigh risk multiple myeloma by molecular profiling: an analysis of newly diagnosed transplant eligible myeloma XI trial patients, LEUKEMIA, Vol: 34, Pages: 3091-3096, ISSN: 0887-6924
- Author Web Link
- Cite
- Citations: 22
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.