ArticleBlood2014
JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 154 citations in OpenAlex.
- Trial
- Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study.Cancer · 2017Trial
- Nilotinib induces immunogenic cuproptosis to potentiate cancer immunotherapy.Cell reports. Medicine · 2026Article
- TIAR-dependent coordination of alternative splicing and lipid peroxidation is required for CML cell resistance to imatinib in the bone marrow stroma.bioRxiv : the preprint server for biology · 2026Article
- IL2RG knockout mitigates polycystic ovary syndrome pathogenesis by transitioning pyroptosis to apoptosis through the GSDME pathway.Journal of ovarian research · 2025Article
- Subclonal emergence of polycythemia vera, chronic myelomonocytic leukemia, and chronic myeloid leukemia.Annals of hematology · 2025Article
- BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia.Cancer science · 2025Article
- Review
- The prospect of substrate-based kinase inhibitors to improve target selectivity and overcome drug resistance.Chemical science · 2024Review
- Advancements and Future Prospects in Molecular Targeted and siRNA Therapies for Chronic Myeloid Leukemia.Biomolecules · 2024Review
- JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib.Disease markers · 2024Article
- Interplay between signal transducers and activators of transcription (STAT) proteins and cancer: involvement, therapeutic and prognostic perspective.Clinical and experimental medicine · 2023Review
- Article
- The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities.Current hematologic malignancy reports · 2023Review
- Induction of DNMT1-dependent demethylation of SHP-1 by the natural flavonoid compound Baicalein overcame Imatinib-resistance in CML CD34Cell communication and signaling : CCS · 2023Article
- Jak2/STAT6/c-Myc pathway is vital to the pathogenicity of Philadelphia-positive acute lymphoblastic leukemia caused by P190Cell communication and signaling : CCS · 2023Article
- Targeting BCR-ABL1-positive leukaemias: a review article.Cambridge prisms. Precision medicine · 2023Review
- Insights from a rare myeloproliferative neoplasm with coexistingClinical case reports · 2023Article
- Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review.Journal of blood medicine · 2023Review
- Therapy Resistance and Disease Progression in CML: Mechanistic Links and Therapeutic Strategies.Current hematologic malignancy reports · 2022Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic myeloid leukemia (CML) stem cell survival is not dependent on BCR-ABL protein kinase and treatment with ABL tyrosine kinase inhibitors cures only a minority of CML patients, thus highlighting the need for novel therapeutic targets. The Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)5 pathway has recently been explored for providing putative survival signals to CML stem/progenitor cells (SPCs) with contradictory results. We investigated the role of this pathway using the JAK2 inhibitor, ruxolitinib (RUX). We demonstrated that the combination of RUX, at clinically achievable concentrations, with the specific and potent tyrosine kinase inhibitor nilotinib, reduced the activity of the JAK2/STAT5 pathway in vitro relative to either single agent alone. These effects correlated with increased apoptosis of CML SPCs in vitro and a reduction in primitive quiescent CML stem cells, including NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice repopulating cells, induced by combination treatment. A degree of toxicity toward normal SPCs was observed with the combination treatment, although this related to mature B-cell engraftment in NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice with minimal effects on primitive CD34(+) cells. These results support the JAK2/STAT5 pathway as a relevant therapeutic target in CML SPCs and endorse the current use of nilotinib in combination with RUX in clinical trials to eradicate persistent disease in CML patients.
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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.