Biology subjects

Hovland, R.

Publications and source records attributed to Hovland, R..

3 recordsLinked to original sources

bioRxiv2023

The Minimal Dataset for Cancer of the 1+Million Genomes Initiative

For a real impact on healthcare, precision cancer medicine requires accessibility and interoperability of clinical and genomic data across centres and countries. Due to the heterogeneous digitization in Europe and worldwide, the definition of models for standardised data collection and usability becomes mandatory if countries want to work together on this mission. The European Union 1+Million Genomes (1+MG) initiative, supported by the Horizon 2020 Beyond 1 Million Genomes project, aims at outlining data models, guidance, best practices, and technical infrastructures for transnational access to sequenced genomes, including cancer genomes. Within the framework of the cancer-focused Working Group 9, we developed the 1+MG-Minimal Dataset for Cancer (1+MG-MDC)-a data model encompassing 140 items and organized in eight conceptual domains for the collection of cancer-related clinical information and genomics metadata. The 1+MG-MDC, which results from a multidisciplinary effort, leverages pre-existing models and emphasizes the annotation and traceability of multiple aspects relevant to the complex longitudinal path of the cancer disease and its treatment. We strived to make the 1+MG-MDC easy to adopt, yet comprehensive, addressing the needs of both clinicians and researchers. We will periodically revise and update it to ensure it remains fit for purpose. We propose the 1+MG-MDC as a model to create homogeneous databases, which would, in turn, guide discussions on clinical and genomic features with prognostic or therapeutic value and foster real-world data research.

cancer biology↗

bioRxiv2019

Proteome and phosphoproteome changes associated with prognosis in acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has therefore become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a 5-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases also could target the factors inducing their upregulation rather than their activity. In conclusion, our study presents markers that could help predict AML relapse and direct therapeutic strategies.

cancer biology↗

bioRxiv2018

Increased Adhesion Of CML Cells By ABL1 Tyrosine Kinase Inhibitors Induce Tunneling Nanotubes

Summary statementThis study describes the effects of tyrosine kinase inhibitors on tunneling nanotube formation via increased adhesion through {beta}-integrin in chronic myeloid leukemia cells.\n\nAbstractThe actin-containing cell-to-cell communicator tunneling nanotube (TNT) is involved in regulation of cell death threshold of leukemic cells, while the mechanism of TNT regulation is mostly unknown. We have investigated TNT formation and its response to treatment in chronic myeloid leukemia (CML) cells with the pathognomonic chimeric fusion kinase BCR-ABL1 after treatment with the tyrosine kinase inhibitor nilotinib and interferon-. Bone marrow cells of chronic phase CML patients and the CML cell line Kcl-22 formed few or no TNTs. Nilotinib and interferon- treatment induced TNT formation in Kcl-22 cells and were found to be linked to increased adherence to fibronectin coated surfaces by restoration of {beta}1-integrin function. This suggests modulation of TNT cell-cell communication in CML as a novel mechanism in kinase inhibitor therapy of CML.

cell biology↗