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.
Results
Showing 1 to 19 of 19 for “"Myeloproliferative neoplasms"”.
-
The molecular pathogenesis of myeloproliferative neoplasms
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of haematological stem cell<br/>malignancies characterised by proliferation of one or more cells of the myeloid lineage. The molecular<br/>investigation of MPN was revolutionized in 2005 by the finding that approximately 95% of cases …
-
Determinants of clinical phenotype in myeloproliferative neoplasms
Background: Myeloproliferative neoplasms, (MPNs) such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized …
-
New molecular and cellular aspects of mutant calreticulin in Myeloproliferative Neoplasms
… thrombocythemia and primary myelofibrosis, two myeloproliferative neoplasms (MPNs) characterised by megakaryocyte hyperplasia. Despite the large body of research built around CALR mutations, many aspects of the oncogenic mechanisms of CALR in MPNs remain unanswered. This investigation aims to …
-
Investigating the anti-leukaemic effect of tamoxifen in the myeloproliferative neoplasms
Myeloproliferative neoplasms (MPNs) commonly result from the acquisition of somatic mutations affecting the Janus kinase 2 (JAK2) (such as JAK2<sup>V617F</sup>) or the multi-functional protein CALR (such as CALR<sup>Ins5</sup> and CALR<sup>Del52</sup>), causing the constitutive activation of signal …
-
Evolution of the genome in myeloproliferative neoplasms and the methylome in blood
… questions pertaining to genomic evolution in myeloproliferative neoplasms (MPNs) and identify changes in the methylome of blood with age and in the context of driver mutations. In the first study, serial sequencing of bulk samples from 30 patients with MPN coupled with clinical data show that …
-
Molecular and functional studies of ABL1 and FGFR1 fusion oncogenes in myeloproliferative neoplasms
… are involved in fusion genes underlying the myeloproliferative neoplasms chronic myeloid leukemia (CML) and the 8p11-myeloproliferative syndrome (EMS). CML and EMS are both myeloproliferative disorders with an initiating, relatively indolent, chronic phase that after some time progresses into …
-
Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms
<p>Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting …
-
Implementation of the JAK2V617F mutation analysis in the pathway of suspected myeloproliferative neoplasms in Groote Schuur Hospital
We studied the implementation of JAK2 mutation analysis in conjunction with the World Health Organisation (WHO) guidelines in the pathway to MPN diagnosis in 279 patients presenting with one of three clinical scenarios: erythrocytosis, OR leukocytosis and/or thrombocytosis and/or splenomegaly; OR …
-
Inferring Clonal Dynamics in Blood using Single-Cell Measurements
… time to ask whether clonally related cells in myeloproliferative neoplasms (MPNs) favor particular blood cell fates. Myeloproliferative neoplasms are clonal disorders driven most frequently by the JAK2-V617F mutation, which arises in a single hematopoietic stem cell (HSC) and ultimately …
-
Modelling timing in blood cancers
… malignancies. Notably, one study has found that Myeloproliferative Neoplasms patients with both JAK2 and TET2 mutations have different disease characteristics with distinct mutation order. My analyses identify HOXA9 as a potential prognosis marker and biological switch responsible for patient …
-
Single-cell approaches reveal functional and molecular heterogeneity in malignant haematopoietic stem cells
… stem cells (HSCs), using JAK2 V617F mutant myeloproliferative neoplasms (MPNs) as a model. This study utilises single-cell gene expression and functional assays to identify a subset of JAK2 V617F mutant HSCs that display defective self-renewal. This defect is rescued by crossing JAK2 V617F …
-
CLINICAL AND LABORATORY CHARACTERISATION OF ACQUIRED VON WILLEBRAND SYNDROME
… diseases such as lymphoproliferative (LPDs) and myeloproliferative neoplasms (MPNs), cardiovascular, and autoimmune conditions. The underlying biological processes differ across clinical contexts and remain incompletely defined, complicating both diagnosis and management. Aim: To characterize …
-
Neuronal regulation of haematopoietic stem cell ageing and age-related blood disorders through the microenvironment
… and restores exacerbated megakaryopoiesis in myeloproliferative neoplasms (MPNs). In summary, these results suggest that HSC niche remodelling and a functional switch of sympathetic activity (β2-AR overriding β3-AR) contribute to myeloid expansion during normal ageing. Certain ageing features …
-
Understanding the role of extrinsic regulators in normal and malignant haematopoiesis
… preleukaemic HSCderived disorders known as the myeloproliferative neoplasms (MPNs). This work identified key regulators of the preleukaemic state, including two potential biomarkers of disease evolution, and additional molecules that associated with advanced disease (Chapter 4). This correlation …
-
Clinical Utility and Impact of Targeted Nucleic Acid Sequencing in Myeloid Malignancies and Precursor Lesions
… including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML), with expanding diagnostic and clinical significance. Given the breadth of genetic aberrations required to diagnose these diseases, higher throughput testing is necessary. Targeted …
-
NOVEL APPROACHES IN GENETIC VARIANT DISCOVERY AND CLASSIFICATION TACKLING UNSOLVED PROBLEMS IN CANCER CLINICAL GENOMICS
… genomics, on ovarian and breast cancers and myeloproliferative neoplasms (MPN) who did not previously show positivity for known MPN genetic drivers (“triple negative disease”). In the latter study, we found a high prevalence of mutations in a known cancer-associated gene, KMT2C. However, we …
-
Detection of the calreticulin type 1 and type 2 mutations in a group of myeloproliferative neoplasm patients using molecular methods
The myeloproliferative neoplasms (MPN), formerly referred to as chronic myeloproliferative disorders, are a group of haematopoietic stem cell disorders that are characterized by clonal proliferation of one or more mature myeloid lineages. The group of disorders, now classified as the classic MPNs, …
-
Identification of Novel Drivers of Haematopoietic Stem Cell Fate Using Low Cell Number Proteomics and Single Cell Profiling
… formation of pre-leukaemic disorders, such as myeloproliferative neoplasms (MPNs), and ultimately to their transformation to acute myeloid leukaemia. Therefore, we urgently require a complete characterisation of the underlying molecular pathways of HSC self-renewal in order to provide crucial …
-
Characterization of 5-methylcytosine dioxygenase Tet2 and rescue of mutant Tet2 activity by using turbo co-substrate
… (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and secondary acute myeloid leukemia derived from these conditions. In cancer cells, the normal regulation of 2-OGDDs activity is disrupted, leading to changes in gene expression and epigenetic modifications. The 2OG …