ArticleBlood2017
Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 77 citations in OpenAlex.
- A phase 2 study of pracinostat combined with ruxolitinib in patients with myelofibrosis.Leukemia & lymphoma · 2019Trial
- Optimized post-GWAS analysis identifies therapeutic targets for essential thrombocythemia and polycythemia vera.Communications medicine · 2026Article
- Sequential treatment with ruxolitinib and imetelstat effectively depletes myelofibrosis hematopoietic stem and progenitor cells.Leukemia · 2026Article
- Polθ activity modulates sensitivity to standard therapies in DNMT3A-deficient leukemia.Cell reports. Medicine · 2026Article
- Give megs a break: minor DNA stress, platelets in excess.Blood advances · 2026Article
- Frequent and clinically relevant germline DNA repair gene variants in young and familial myeloproliferative neoplasms.Blood cancer journal · 2026Article
- Article
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
- PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks.Nature communications · 2024Article
- Article
- Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.Cell death & disease · 2024Article
- Differential properties of Janus kinase inhibitors in the treatment of immune-mediated inflammatory diseases.Rheumatology (Oxford, England) · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Exploiting Synthetic Lethality between Germline BRCA1 Haploinsufficiency and PARP Inhibition in JAK2V617F-Positive Myeloproliferative Neoplasms.International journal of molecular sciences · 2023Article
- Simultaneous Targeting of DNA Polymerase Theta and PARP1 or RAD52 Triggers Dual Synthetic Lethality in Homologous Recombination-Deficient Leukemia Cells.Molecular cancer research : MCR · 2023Article
- Calreticulin as a marker and therapeutic target for cancer.Clinical and experimental medicine · 2023Review
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- Article
- Article
- 3D-QSAR, molecular docking, and molecular dynamics analysis of dihydrodiazaindolone derivatives as PARP-1 inhibitors.Journal of molecular modeling · 2023Article
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Authors and funding
20 authors at 9 institutions in 7 countries.
Funding
Abstract
Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673. At the same time, primary MPN cell samples from individual patients displayed a high degree of variability in sensitivity to these drugs. Ruxolitinib inhibited 2 major DSB repair mechanisms, BRCA-mediated homologous recombination and DNA-dependent protein kinase-mediated nonhomologous end-joining, and, when combined with olaparib, caused abundant accumulation of toxic DSBs resulting in enhanced elimination of MPN primary cells, including the disease-initiating cells from the majority of patients. Moreover, the combination of BMN673, ruxolitinib, and hydroxyurea was highly effective in vivo against JAK2(V617F)
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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.