Project description:Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal disorders characterized by aberrant hematopoietic proliferation and an intrinsic risk of progression to blast phase. The WHO classification 2022 identifies chronic myeloid leukemia and the BCR::ABL1 negative MPNs polycythemia vera, primary myelofibrosis and essential thrombocythemia as individual entities. However, overlaps, borderline findings or transitions between MPN subtypes occur and incomplete clinical data often complicates diagnosis. By conducting a thorough genetic analysis, we've developed a model that relies on 12 genetic markers to accurately stratify MPN patients. The model can be simplified into a decision tree for routine use. Comparing samples at chronic and blast phase revealed, that one third of patients lost their MPN driver-gene mutation, while mutations in splicing and chromatin modifying genes were stable, indicating a shared founder clone of chronic and blast phase with different driver mutations and therefore different progressing capacities. This was further supported by gain of typical de novo AML gene mutations, accompanied by gain of complex karyotypes and RAS pathway gene mutations. Our data suggest to perform a broader genetic screening at diagnosis and also at clinical progression, as driver mutations may change and the MPN driver mutations present at diagnosis may disappear.
Project description:Experiments using targeted pulldown methods will be sequenced to validate findings in the exomes of patients with Myeloproliferative Neoplasms (MPN).
Project description:Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) In this dataset, we compare the gene expression data of patients JAK2V617F vs. CALR-mutated MPN patients.
Project description:To elucidate the mechanisms underlying the pathogenic role of Gadd45g deficiency in myeloproliferative neoplasms, we performed RNA sequencing on c-kit+ BM cells from heterozygous Gadd45g knockout mice with MPN and those from Ctrl mice.
Project description:Patients with chronic Myeloproliferative Neoplasms (MPN) including polycythaemia vera (PV) and essential thrombocythemia (ET) exhibit unique clinical features, such as a tendency toward thrombosis and hemorrhage, and risk of disease progression to secondary bone marrow fibrosis and/or acute leukemia. Although an increase in blood cell lineage counts (quantitative features) contribute to these morbid sequelae, the significant qualitative abnormalities of myeloid cells that contribute to vascular risk are not well understood. Here, we address this critical knowledge gap via a comprehensive and untargeted profiling (using label free quantitative mass spectrometry) of the platelet proteome in a large (n= 140) cohort of patients (from two independent sites) with an established diagnosis of PV and ET. We discover distinct MPN platelet protein expression and confirm key molecular impairments associated with proteostasis and thrombosis mechanisms of potential relevance to MPN pathology.
Project description:Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) and seconday myelofibrosis (SMF), comprising post-ET-MF(pET-MF) and post-PV-MF(pPV-MF). In this dataset, we compare the gene expression data of bone marrow or peripheral blood mononuclear cells (BMMCs/PBMCs) of CD34+ cells from MPN patients and healthy donors.
