Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 15 of 15 for “"Clonal haematopoiesis"”.
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The natural history of clonal haematopoiesis
… throughout life, some of which can drive clonal expansion. Such expansions are frequent in the haematopoietic system of healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other diseases, we have limited understanding of its …
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Modelling the age-dependent dynamics of clonal haematopoiesis
… stem cells, this process, known as clonal haematopoiesis (CH), can often be detected years before the onset of haematological cancer, raising the possibility that individual cancer risk could be inferred from a routine blood sample. While recent studies have begun to quantify CH …
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The role of the Dnmt3aR882H mutation in the evolution of clonal haematopoiesis.
DNMT3A mutations are very frequent events in clonal haematopoiesis of indeter- minate potential (CHIP), and considered one of the earliest genetic events during the development of haematopoietic malignancies. Individuals with CHIP, in spite of having a normal full blood count are at increased risk …
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Mechanisms driving the expansion and progression of splicing factor-mutant clonal haematopoiesis
Clonal haematopoiesis (CH) describes the expansion of haematopoietic stem cells (HSCs) and their progeny due to the acquisition of somatic mutations. CH can be detected almost ubiquitously with advancing age and is associated with an increased risk of incident haematological malignancy and several …
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Trees and Forests: Data Science and Machine Learning Approaches to Characterise Clonal Haematopoiesis
Clonal haematopoiesis (CH), the expansion of a haematopoietic stem cell (HSC) driven by somatic mutations in leukaemia-associated genes, is a common age-related phenomenon that affects more than 20% of adults aged over 70 years. As the shared precursor of most myeloid neoplasms (MN), timely …
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The evolutionary dynamics of clonal haematopoiesis and its progression to acute myeloid leukaemia
… difficulties with early detection of AML is that clonally expanded leukaemia-associated mutations are also found in the blood of healthy individuals, a phenomenon termed ‘clonal haematopoiesis’. However, most individuals with clonal haematopoiesis will never progress to AML and so a key challenge …
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Clonal haematopoiesis of indeterminate potential and the role of inflammation in its association with atherosclerosis
… inflammation in ageing remains unclear. Clonal haematopoiesis of indeterminate potential (CHIP) is a common age-associated condition in which haematopoietic stem cells acquire somatic mutations, leading to clonal expansion and aberrant cellular functions. CHIP has been suggested to drive …
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The pre-clinical evolution of haematological malignancies
… somatic mutations frequently drive clonal expansions in normal ageing tissues. However, the factors governing whether pre-cancerous cells transform into cancer are poorly understood, hindering identification of clones that are clinically significant rather than benign sequelae of …
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Computational analyses of blood cells: somatic evolution and morphology
Haematopoiesis is the complex process of blood cell production, carried out by haematopoietic stem cells in the bone marrow. Over the human lifespan, it generates quadrillions of cells which participate in essential bodily functions such as immunity (whiteblood cells), oxygen distribution (red …
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Detection, causes and consequences of sex chromosome mosaicism
… chromosome X (LOX), is the most common form of clonal haematopoiesis (CH) that can be defined as the age-related clonal expansion of blood cells with somatic mutations. With the decreased cost of sequencing, the development of new bioinformatics methods and the emergence of large cohorts with …
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Resolving the evolution of Oesophageal Adenocarcinoma using spatial and temporal sampling
… in OAC, with the majority of mutations being subclonal. Moreover, SMAD4 which has been previously shown to be a biomarker for poor prognosis, was more often subclonal. In addition, the majority of the BO mutations are also subclonal, indicating substantial ITH in this premalignant lesion. As …
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The Effects of Methyltransferase Genes on Human Haematopoietic Stem Cell Function
… lie intermingled with wild type (WT) HSCs. Clonal expansion of HSCs is an ineluctable feature of advancing age, and age related clonal haematopoiesis (ARCH) is associated with an increased risk of haematological malignancy, atherosclerosis and cardiovascular disease. The functional effects …
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Clonal dynamics of haematopoiesis across the human lifespan
… or blood loss; and increased risk of clonal haematopoiesis and blood cancers. The cellular alterations that underpin these age-related phenotypes, which typically manifest in individuals aged over 70, remain elusive. In my thesis I have aimed to investigate whether changes in HSC …
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Gene expression profiling of patients with Polycythaemia Rubra Vera using cDNA microarrays
… these cells yield high amounts of RNA and arise clonally from the aberrant stem cell. In order to identify genes which are specifically altered in PV, RNA from purified granulocytes of 10 patients with SE and 10 PV patients was hybridised to a control RNA pool consisting of total granulocyte RNA …
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Quantitative Analyses of Normal and Precancerous Somatic Evolution in Human Tissues
… in using evolutionary histories revealed by clonal trees to separate out parametrical influence of the two major parameters µ and s in preleukemic evolution. We showed that the k-hit staircase model makes many tractable predictions regarding variation across individuals and large variations …