ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Broad Next-Generation Integrated Sequencing of Myelofibrosis Identifies Disease-Specific and Age-Related Genomic Alterations.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 8 citations in OpenAlex.
- U2af1Leukemia · 2026Article
- Thrombopoietin Receptor MPL in Hematopoiesis and Myeloproliferative Neoplasms: Physiological Roles and Pathogenic Mechanisms.Stem cell reviews and reports · 2026Review
- A stem and progenitor cell-derived gene expression signature is prognostic for survival in myelofibrosis.Blood · 2026Article
- Clonal megakaryocyte dysplasia with normal blood values: a covert, thrombosis-prone, early myeloproliferative neoplasm.Haematologica · 2026Article
- Integrated transcriptome-proteome analysis in patients with myelofibrosis-related anemia.Annals of hematology · 2026Article
- Single-cell RNA sequencing of platelets: challenges and potential.Journal of thrombosis and thrombolysis · 2026Article
- [Efficacy of ruxolitinib and prognostic factors in patients with myelofibrosis stratified by age].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Exploring common mechanisms of adverse drug reactions and disease phenotypes through network-based analysis.Cell reports methods · 2025Article
- Fusion Genes in Myeloid Malignancies.Cancers · 2024Review
- Bibliometric analysis of worldwide research on Polycythemia Vera in the 21st century.Annals of hematology · 2024Review
- DREAMER: Exploring Common Mechanisms of Adverse Drug Reactions and Disease Phenotypes through Network-Based Analysis.bioRxiv : the preprint server for biology · 2024Article
- Exploring the Molecular Landscape of Myelofibrosis, with a Focus on Ras and Mitogen-Activated Protein (MAP) Kinase Signaling.Cancers · 2023Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeMyeloproliferative neoplasms (MPN) are characterized by the overproduction of differentiated myeloid cells. Mutations in JAK2, CALR, and MPL are considered drivers of Bcr-Abl-ve MPN, including essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic primary myelofibrosis (prePMF), and overt myelofibrosis (MF). However, how these driver mutations lead to phenotypically distinct and/or overlapping diseases is unclear. EXPERIMENTAL
designTo compare the genetic landscape of MF to ET/PV/PrePMF, we sequenced 1,711 genes for mutations along with whole transcriptome RNA sequencing of 137 patients with MPN.
resultsIn addition to driver mutations, 234 and 74 genes were found to be mutated in overt MF (N = 106) and ET/PV/PrePMF (N = 31), respectively. Overt MF had more mutations compared with ET/PV/prePMF (5 vs. 4 per subject, P = 0.006). Genes frequently mutated in MF included high-risk genes (ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1) and Ras pathway genes. Mutations in NRAS, KRAS, SRSF2, EZH2, IDH2, and NF1 were exclusive to MF. Advancing age, higher DIPSS, and poor overall survival (OS) correlated with increased variants in MF. Ras mutations were associated with higher leukocytes and platelets and poor OS. The comparison of gene expression showed upregulation of proliferation and inflammatory pathways in MF. Notably, ADGRL4, DNASE1L3, PLEKHGB4, HSPG2, MAMDC2, and DPYSL3 were differentially expressed in hematopoietic stem and differentiated cells.
conclusionsOur results illustrate that evolution of MF from ET/PV/PrePMF likely advances with age, accumulation of mutations, and activation of proliferative pathways. The genes and pathways identified by integrated genomics approach provide insight into disease transformation and progression and potential targets for therapeutic intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.