A5059876373- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Advanced Breast Cancer Therapies
- Acute Myeloid Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Crafts, Textile, and Design
- Hematopoietic Stem Cell Transplantation
- Viral-associated cancers and disorders
- Fashion and Cultural Textiles
- Biochemical and Molecular Research
- Genomic variations and chromosomal abnormalities
- Immune Cell Function and Interaction
- Renal Transplantation Outcomes and Treatments
- Pancreatic and Hepatic Oncology Research
- HIV/AIDS drug development and treatment
- Hemoglobinopathies and Related Disorders
- Cancer-related Molecular Pathways
- Eosinophilic Disorders and Syndromes
- Cerebrovascular and genetic disorders
University Hospital Limerick
2018-2024
University of Limerick
2022-2024
San Jose State University
2024
Heidelberg University
2022
University of Oxford
1978-2020
National Institute for Health Research
2012-2020
Oxford University Hospitals NHS Trust
2014-2018
University of Lahore
2017
Pir Mehr Ali Shah Arid Agriculture University
2017
John Radcliffe Hospital
2012-2016
Abstract The value of genome-wide over targeted driver analyses for predicting clinical outcomes cancer patients is debated. Here, we report the whole-genome sequencing 485 chronic lymphocytic leukemia enrolled in trials as part United Kingdom’s 100,000 Genomes Project. We identify an extended catalog recurrent coding and noncoding genetic mutations that represents a source future studies provide most complete high-resolution map structural variants, copy number changes global genome...
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and disrupted at the genomic level in a spectrum human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions SETD2 locus 3% (8/261) chronic lymphocytic leukaemia (CLL) patients. Further validation two independent cohorts showed that were associated with loss TP53, complexity chromothripsis. With...
Chronic lymphocytic leukaemia (CLL) consists of two biologically and clinically distinct subtypes defined by the abundance somatic hypermutation (SHM) affecting Ig variable heavy-chain locus (IgHV). The molecular mechanisms underlying these are incompletely understood. Here, we present a comprehensive whole-genome sequencing analysis somatically acquired genetic events from 46 CLL patients, including systematic comparison coding non-coding single-nucleotide variants, copy number variants...
Genome-wide array approaches and sequencing analyses are powerful tools for identifying genetic aberrations in cancers, including leukemias lymphomas. However, the clinical biological significance of such their subclonal distribution poorly understood. Here, we present first genome-wide based study pre-treatment relapse samples from patients with B-cell chronic lymphocytic leukemia (B-CLL) that uses computational statistical tool OncoSNP. We show quantification proportion copy number...
Richter syndrome ( RS ) is associated with chemotherapy resistance and a poor historical median overall survival OS of 8–10 months. We conducted phase II trial standard CHOP ‐21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) ofatumumab induction (Cycle 1: 300 mg day 1, 1000 8, 15; Cycles 2–6: 1) ‐O) followed by 12 months maintenance (1000 given 8‐weekly for up to six cycles). Forty‐three patients were recruited whom 37 evaluable. Seventy‐three per cent aged >60...
Abstract Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with trials representing an invaluable resource to explore disease-related/genetic features contributing long-term outcomes. In 499 LRF CLL4 cases, trial >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6%...
Aims Richter's syndrome ( RS ) refers to high‐grade transformation of B‐cell chronic lymphocytic leukaemia CLL ), usually diffuse large lymphoma, as assessed according strict World Health Organization WHO )‐defined histological criteria. Although this is a relatively evidence‐poor area, the recommended clinical management differs considerably from that relapsed . The ‘ CHOP ‐ OR ’ trial was single‐arm, multicentre, non‐randomized phase II National Cancer Research Institute in patients with...
Abstract Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, often co-expressed light IgLV3-21, which potentially able to trigger cell-autonomous BCR-mediated signaling. However, this has never been characterized independently of the IgHV3-21. Experimental Design: We performed total RNA sequencing 32 patients and investigated IgLV3-21 prognostic...
Abstract Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage into naive B-cell–like CLL (n-CLL), memory (m-CLL), and intermediate (i-CLL), differing times first treatment overall survival. However, whether identify destined favorably CIT has not been ascertained. We classified treatment-naive (n =...
There is a need in clinical tetanus for simple prognostic classification all patients at time of admission to the hospital. Data from three randomized trials performed India 1960s, which contained information on several variables 1,385 patients, have been used study different methods prognosis. A logistic regression combined data suggested that probability death related separately period onset (the first symptom generalized reflex spasms), hospital, and assessment severity admission; effects...
To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired to fludarabine-based chemotherapy represents a major challenge long-term disease control.We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, genes that confer human CLL cell line.In total, this screen identified 782 transposon integrations fludarabine-resistant pools of cells. One is known mediator DCK (deoxycytidine...
Summary Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front‐line ‘attenuated’ or low‐intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report of attenuated 95 with MCL across 19 centres the UK and Ireland considered for full‐dose rituximab‐bendamustine rituximab‐cyclophosphamide, doxorubicin, vincristine, prednisolone (R‐CHOP). Regimens examined were (R‐CVP) ( n = 19), dose‐attenuated R‐CHOP...
Summary The 100 000 Genome Project aims to develop a diagnostics platform by introducing whole genome sequencing (WGS) into clinical practice. Samples from patients with chronic lymphocytic leukaemia were subjected WGS. WGS detection of single nucleotide variants and insertion/deletions validated targeted next generation showing high concordance (96·3%), also for sub‐clonal low‐frequency TP53 variants. Copy number alteration was verified fluorescent in situ hybridisation genome‐wide...
Transformation of B-cell chronic lymphocytic leukaemia (B-CLL) to diffuse large B cell lymphoma (DLBCL) (Richter's syndrome (RS)) is a rare (2-15% patients) but catastrophic complication B-CLL. Dose-intense chemotherapy regimens investigated in small single institution trials, with the exception bone marrow transplantation for minority patients, little has improved median overall survival patients RS beyond eight months. Patients are often elderly, immunosuppressed, possess co-morbidities...
Genomic tests may improve the stratification of patients to receive new therapies in several disease areas. However, use expensive targeted can impact on cost effectiveness these tests. This study presents an economic evaluation genomic testing chronic lymphocytic leukaemia context UK National Health Service.Cost-effectiveness and cost-utility analyses (using life-years quality-adjusted life-years) were undertaken from a Service societal perspective. Five strategies evaluated across age...