Publications
420 results found
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
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- Citations: 41
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
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- Citations: 4
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
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- Citations: 192
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
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- Citations: 2
Claudiani S, Mason CC, Milojkovic D, et al., 2021, Carfilzomib Enhances the Suppressive Effect of Ruxolitinib in Myelofibrosis, CANCERS, Vol: 13
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- Citations: 1
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
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- Citations: 17
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
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
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- Citations: 13
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
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- Citations: 24
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
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- 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
Medani H, Elshiekh M, Naresh K, 2020, Accurate Mitotic Counts in Mantle Cell Lymphoma Using Phosphohistone H3 (PHH3) Immunohistochemistry, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: NATURE PUBLISHING GROUP, Pages: 1346-1347, ISSN: 0023-6837
Medani H, Sayed A, Cooper N, et al., 2020, Bone Marrow Trephine Biopsy in Patients of Primary Immune Thrombocytopenia on Treatment with Thrombopoietin Receptor Agonists, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: NATURE PUBLISHING GROUP, Pages: 1348-1348, ISSN: 0023-6837
Medani H, Sayed A, Cooper N, et al., 2020, Bone Marrow Trephine Biopsy in Patients of Primary Immune Thrombocytopenia on Treatment with Thrombopoietin Receptor Agonists, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: SPRINGERNATURE, Pages: 1348-1348, ISSN: 0893-3952
Medani H, Elshiekh M, Naresh K, 2020, Accurate Mitotic Counts in Mantle Cell Lymphoma Using Phosphohistone H3 (PHH3) Immunohistochemistry, 109th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), Publisher: SPRINGERNATURE, Pages: 1346-1347, ISSN: 0893-3952
Ponnusamy K, Tzioni M-M, Begum M, et al., 2019, Novel ZBP1-IRF3 Dependency in Multiple Myeloma Mediated By IRF3-Driven Regulation of Cell Cycle Genes, BLOOD, Vol: 134, ISSN: 0006-4971
Bewicke-Copley F, Korfi K, Araf S, et al., 2019, Longitudinal Analyses of Diagnostic-Relapse Biopsies of Diffuse Large B Cell Lymphoma Reveal a Poor Risk Subset of ABC Patients Based on the Expression of a 30 Gene Panel, BLOOD, Vol: 134, ISSN: 0006-4971
Li X, Kositsky R, Reddy A, et al., 2019, Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma, BLOOD, Vol: 134, ISSN: 0006-4971
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- Citations: 1
Trasanidis N, Katsarou A, Bergonia B, et al., 2019, PBX1 Co-Operates with FOXM1 to Regulate Myeloma Cell Proliferation and to Define an Ultra High-Risk chr1q Gain Myeloma Patient Subgroup, BLOOD, Vol: 134, ISSN: 0006-4971
Elliott T, Simpson J, Naresh KN, et al., 2019, An unusual case of post-kala-azar dermal leishmaniasis in a patient with HIV and visceral leishmaniasis co-infection, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 30, Pages: 1221-1223, ISSN: 0956-4624
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- Citations: 2
Khan M, Naresh K, Krell J, et al., 2019, A challenging case of indeterminate cell histiocytosis with only partial response treatment., 16th International Workshop on Langerhans Cells (LC), Publisher: WILEY, Pages: 18-19, ISSN: 0014-2980
El-Sharkawi D, Sharma S, Cook L, et al., 2019, Comparison of Outcomes Between Patients with <i>MYC</i> Rearranged DLBCL and Double/Triple Hit High-Grade B-Cell Lymphoma: A Pan-London Retrospective Review, Publisher: CIG MEDIA GROUP, LP, Pages: S248-S248, ISSN: 2152-2650
Hanley BP, Naresh KN, 2019, Evolution of Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma, 12th Joint Meeting of the British-Division-of-the-International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland (Leeds Pathology), Publisher: WILEY, Pages: S42-S42, ISSN: 0022-3417
Elshiekh M, Lippert T, Dalla Pria A, et al., 2019, PDL1 and PDL2 Expression in Plasmablastic and Primary Effusion Lymphomas, 12th Joint Meeting of the British-Division-of-the-International-Academy-of-Pathology and the Pathological-Society-of-Great-Britain-and-Ireland (Leeds Pathology), Publisher: WILEY, Pages: S18-S18, ISSN: 0022-3417
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