ArticleNature communications2025
RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- Molecular Response, Event-Free Survival, and Treatment-Free Remission in Myeloproliferative Neoplasms: Update and Review with Insights from MPN Asia 2026.Current hematologic malignancy reports · 2026Review
- A patent perspective of RSK inhibitors to treat cancer (2020-present).Expert opinion on therapeutic patents · 2026Review
- Selective targeting of RSK signaling with PMD-026 suppresses FLT3-activated acute myeloid leukemia while sparing normal hematopoiesis.Leukemia · 2026Article
- Single-cell long-read genotyping of transcripts reveals discrete mechanisms of clonal evolution in post-MPN AML.Blood advances · 2026Article
- A stem and progenitor cell-derived gene expression signature is prognostic for survival in myelofibrosis.Blood · 2026Article
- FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.iScience · 2026Article
- RPS6KA1 Remodels Fatty Acid Metabolism and Suppresses Malignant Progression in Colorectal Cancer.Biomedicines · 2026Article
- A novel anoikis resistance-associated gene model for prognostic prediction and immune microenvironment characterization in lung squamous cell carcinoma.Discover oncology · 2026Article
- RSK signaling in myeloid malignancies: biology, disease dependency, and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies.Cell communication and signaling : CCS · 2025Article
- Expansion characteristics of CD34Human cell · 2025Article
- Review
- Monocyte Involvement in the Pathogenesis of Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- RSK1 dependency in FLT3-ITD acute myeloid leukemia.Blood cancer journal · 2024Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation. Combining ATAC-Seq, CUT&Tag, RNA-seq, and CyTOF, we demonstrate that targeting of ribosomal protein S6 kinase A1 (RSK1) suppresses NFκB activation and diminishes pro-inflammatory mediators including tumor necrosis factor (TNF) associated with MPN disease severity and transformation. We further evaluate a therapeutic approach utilizing a first-in-class RSK inhibitor, PMD-026, currently in Phase 2 development for breast cancer, for use in myeloid malignancies. Treatment with PMD-026 suppressed disease burden across seven syngeneic and patient-derived xenograft leukemia mouse models spanning the spectrum of driver and disease-modifying mutations. These findings uncover a therapeutic avenue for a conserved dependency across MPN and sAML.
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Registered trials
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 Socratic graph.