A5024188669- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Retinoids in leukemia and cellular processes
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Hematopoietic Stem Cell Transplantation
- Heat shock proteins research
- Molecular Biology Techniques and Applications
- Immune cells in cancer
- S100 Proteins and Annexins
- Vascular Tumors and Angiosarcomas
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
Cardiff University
2015-2024
University College London
2005-2018
Queen Mary University of London
2018
Newcastle upon Tyne Hospitals NHS Foundation Trust
2018
North Bristol NHS Trust
2018
University Hospital of Wales
2005-2016
Fred Hutch Cancer Center
2015
Seagen (United States)
2015
Cancer Research Center
2015
University of Wales
1998-2011
Despite the molecular heterogeneity of standard-risk acute myeloid leukemia (AML), treatment decisions are based on a limited number genetic markers and morphology-based assessment remission. Sensitive detection leukemia-specific marker (e.g., mutation in gene encoding nucleophosmin [NPM1]) could improve prognostication by identifying submicroscopic disease during
The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories myeloid and lymphoid malignancies.The investigation was performed 11 laboratories across three continents included 3,334 patients. An exploratory retrospective stage I designed for biomarker discovery generated whole-genome profiles from 2,143 patients with myelodysplastic syndromes. profiling-based diagnostic accuracy...
Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate extent its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other response criteria. Methods As part NCRI AML17 trial, 2,450 younger adult patients AML high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After 1 (C1),...
Abstract Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize validate 16 classes describing 100% AML Each class represents diverse biological subgroups, is associated with distinct clinical presentation, likelihood response to induction chemotherapy, risk relapse...
To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics.
Summary Gene expression profiling has the potential to enhance current methods for diagnosis of haematological malignancies. Here, we present data on 204 analyses from an international standardization programme that was conducted in 11 laboratories as a prephase Microarray Innovations LEukemia (MILE) study. Each laboratory prepared two cell line samples, together with three replicate leukaemia patient lysates distinct stages: (i) 5‐d course protocol training, and (ii) independent proficiency...
Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3-internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD-negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older AML genotype. Therefore, we examined the impact of age on prognostic significance status in AML.
Abstract Patients with FLT3 -mutated AML have a high relapse rate and suboptimal outcomes. Many co-mutations suitable for measurable residual disease (MRD) monitoring by RT-qPCR those destined to can be identified or rising levels of MRD, called molecular failure. This provides window pre-emptive intervention, but there is little evidence guide treatment. The use inhibitors (FLT3i) appears attractive their has not yet been evaluated. We 56 patients treated FLT3i at mutation was an ITD in 52,...
NPM 1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of "therapy-related" NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared genetics, transcriptional profile, and clinical outcomes t-NPM1 AML, de novo (dn-NPM1 AML), therapy-related (t-AML) with wild-type NPM1 (t-AML). Normal karyotype was more frequent in (n = 78/96, 88%) dn-NPM1 1986/2394, than t-AML 103/390, 28%; P < .001). DNMT3A TET2 were mutated 43% 40% 107), similar to 88, 48%...
Liposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients secondary acute myeloid leukemia (AML); to date, there have been no randomized studies younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) CPX-351 FLAG-Ida adults newly diagnosed adverse cytogenetic AML or myelodysplastic syndromes (MDS). A total 189 were (median age, 56 years). Per clinical criteria, 49% had de novo AML, 20% 30% MDS....
Abstract Addition of gemtuzumab ozogamicin (GO) to induction chemotherapy improves outcomes in older patients with acute myeloid leukemia (AML), but it is uncertain whether a fractionated schedule provides additional benefit single dose. We randomized 852 adults (median age, 68-years) AML/high-risk myelodysplasia GO on day 1 (GO1) or days and 4 (GO2) course induction. The median follow-up period was 50.2 months. Although complete remission (CR) rates after did not significantly differ...
PURPOSE AML is a genetically heterogeneous disease, particularly in older patients. In patients than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there an urgent need clinical practice for prognostic model to identify with who benefit from treatment. METHODS We studied 1,910 intensively treated years and high-risk myelodysplastic syndrome (HR-MDS) two...
Abstract Inappropriate localization of proteins can interfere with normal cellular function and drive tumor development. To understand how this contributes to the development acute myeloid leukemia (AML), we compared nuclear proteome transcriptome AML blasts human CD34 + cells. Analysis identified networks processes that significantly affected transcription regulation including misexpression 11 factors seven not previously implicated in AML. Transcriptome analysis changes 40 but none these...