Next-generation sequencing for patients with myelofibrosis
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ABSTRACT:
PROVIDER: PRJEB40346 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Determination of differentially expressed genes from peripheral blood of Myelofibrosis patients with JAK2VF and JAK2VF and DNMT3A mutations
2018-12-01 | E-MTAB-7255 | biostudies-arrayexpress
Project description:Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow sclerosis, extra-medullary hematopoiesis, and possible transformation to acute leukemia. In the last decade, the molecular pathogenesis of the disease has been largely uncovered. Particularly, genetic and genomic studies have provided evidence of deregulated oncogenes in PMF as well as in other MPNs. However, the mechanisms through which transformation to either the myeloid or lymphoid blastic phase remain obscure. Particularly, it is still debated whether the disease has origins in a multi-potent hematopoietic stem cells or instead in a commissioned myeloid progenitor. In this study, we aimed to shed light upon this issue by using next generation sequencing (NGS) to study both myeloid and lymphoid cells as well as matched non-neoplastic DNA of PMF patients. Whole exome sequencing revealed that most somatic mutations were the same between myeloid and lymphoid cells, such findings being confirmed by Sanger sequencing. Particularly, we found 126/146 SNVs to be the e same (including JAK2V617F), indicating that most genetic events likely to contribute to disease pathogenesis occurred in a non-commissioned precursor. In contrast, only 9/27 InDels were similar, suggesting that this type of lesion contributed instead to disease progression, occurring at more differentiated stages, or maybe just represented "passenger" lesions, not contributing at all to disease pathogenesis. In conclusion, we showed for the first time that genetic lesions characteristic of PMF occur at an early stage of hematopoietic stem cell differentiation, this being in line with the possible transformation of the disease in either myeloid or lymphoid acute leukemia.
| S-EPMC10046249 | biostudies-literature
Project description:RNA-seq of JAK2VF and DNMT3A mutant Myelofibrosis patients
| PRJEB28858 | ENA
Project description:NGPS is a method for de-novo, full-length protein sequencing in high throughput. The method is based on cleavage of the protein at semi-random sites by microwave-assisted acid hydrolysis (MAAH), enrichment of LC-MS/MS amenable peptides from the hydrolysate by solid-phase-extraction, LC-MS/MS analysis, de-novo long peptide tag sequencing of resulting peptides and assembly of peptide tags into consensus contigs.
2017-04-03 | PXD003804 | Pride
Project description:Patient samples were analysed for the presence of genomic aberrations prior to ABMT and following relapse, in case it occurred, in patients with primary myelofibrosis.
2020-11-29 | E-MTAB-9110 | biostudies-arrayexpress
Project description:We performed single cell DNA sequencing by means of Tapestri platform on a mix of Peripheral Blood Mononuclear Cells (PBMCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs) from a primary myelofibrosis (PMF). The main purpose of this project was to reconstruct the clonal composition of the neoplastic population by analyzing the mutational profile at the single-cell level.
2024-10-15 | GSE251689 | GEO
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders Transcriptome analysis was performed on BM-MSC amplified in vitro after 3 to 5 passages. Agilent Whole Human Genome Oligo Microarrays were used to compare expression profiling of BM-MSC from PMF patients and healthy donors.
2015-01-10 | E-GEOD-44426 | biostudies-arrayexpress
Project description:Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis, and a propensity towards transformation to acute leukemia. JAK inhibitors are the only approved therapy for myelofibrosis and have been successful in reducing spleen and symptom burden. However, they do not significantly impact disease progression and many patients are ineligible due to coexisting cytopenias. Patients who are refractory to JAK inhibition also have a dismal survival. Therefore, non-JAK inhibitor-based therapies are being explored in pre-clinical and clinical settings. In this review, we discuss novel treatments in development for myelofibrosis with targets outside of the JAK-STAT pathway. We focus on the mechanism, preclinical rationale, and available clinical efficacy and safety information of relevant agents including those that target apoptosis (navitoclax, KRT-232, LCL-161, imetelstat), epigenetic modulation (CPI-0610, bomedemstat), the bone marrow microenvironment (PRM-151, AVID-200, alisertib), signal transduction pathways (parsaclisib), and miscellaneous agents (tagraxofusp. luspatercept). We also provide commentary on the future of therapeutic development in myelofibrosis.
| S-EPMC8146033 | biostudies-literature
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders
2015-01-10 | GSE44426 | GEO
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neo-osteogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic cells and the osteoblastic niche is deregulated in the PMF BM microenvironment. Osteoblastic niche is well known to be an important support to regulate hematopoietic stem cell functions in bone marrow. A transcriptome analysis of bone marrow mesenchymal stem cells (BM-MSC) induced in vitro to differentiate in osteoblasts will help to understand the role of these cells in pathophysiology of PMF. Transcriptome analysis was performed on BM-MSC at J0 and J21 of in vitro osteoblastic differentiation. Agilent Whole Human Genome Oligo Microarrays were used to compare expression profiling of BM-MSCs from PMF patients and healthy donors before and after osteoblastic differentiation. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders
2015-01-10 | E-GEOD-46021 | biostudies-arrayexpress