ArticleJournal of cellular and molecular medicine2013
Combination treatment for myeloproliferative neoplasms using JAK and pan-class I PI3K inhibitors.
Article in Journal of cellular and molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.American journal of hematology · 2025Review
- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- FOXA1 prolongs S phase and promotes cancer progression in non-small cell lung cancer through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.The Kaohsiung journal of medical sciences · 2023Article
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
- A lymphatic-absorbed multi-targeted kinase inhibitor for myelofibrosis therapy.Nature communications · 2022Article
- Understanding Aberrant Signaling to Elude Therapy Escape Mechanisms in Myeloproliferative Neoplasms.Cancers · 2022Review
- The delta isoform of phosphatidylinositol-3-kinase predominates in chronic myelomonocytic leukemia and can be targeted effectively with umbralisib and ruxolitinib.Experimental hematology · 2021Article
- Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks.NAR genomics and bioinformatics · 2021Article
- Challenges and Perspectives for Therapeutic Targeting of Myeloproliferative Neoplasms.HemaSphere · 2021Review
- Cotargeting the JAK/STAT signaling pathway and histone deacetylase by ruxolitinib and vorinostat elicits synergistic effects against myeloproliferative neoplasms.Investigational new drugs · 2020Article
- Article
- Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Review
- IL-6 stimulation of DNA replication is JAK1/2 mediated in cross-talk with hyperactivated ERK1/2 signaling.Cell biology international · 2019Article
- Leveraging JAK-STAT regulation in myelofibrosis to improve outcomes with allogeneic hematopoietic stem-cell transplant.Therapeutic advances in hematology · 2018Review
- New therapeutic options opened by the molecular classification of gastric cancer.World journal of gastroenterology · 2018Review
- JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders.F1000Research · 2018Review
- Inhibitors of the PI3K/mTOR pathway prevent STAT5 phosphorylation inOncotarget · 2017Article
- Activating JAK2 mutants reveal cytokine receptor coupling differences that impact outcomes in myeloproliferative neoplasm.Leukemia · 2017Article
- Epigenetics in Myeloproliferative Neoplasms.Journal of cellular and molecular medicine · 2017Review
- Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current JAK2 inhibitors used for myeloproliferative neoplasms (MPN) treatment are not specific enough to selectively suppress aberrant JAK2 signalling and preserve physiological JAK2 signalling. We tested whether combining a JAK2 inhibitor with a series of serine threonine kinase inhibitors, targeting nine signalling pathways and already used in clinical trials, synergized in inhibiting growth of haematopoietic cells expressing mutant and wild-type forms of JAK2 (V617F) or thrombopoietin receptor (W515L). Out of 15 kinase inhibitors, the ZSTK474 phosphatydylinositol-3'-kinase (PI3K) inhibitor molecule showed strong synergic inhibition by Chou and Talalay analysis with JAK2 and JAK2/JAK1 inhibitors. Other pan-class I, but not gamma or delta specific PI3K inhibitors, also synergized with JAK2 inhibitors. Synergy was not observed in Bcr-Abl transformed cells. The best JAK2/JAK1 and PI3K inhibitor combination pair (ruxolitinib and GDC0941) reduces spleen weight in nude mice inoculated with Ba/F3 cells expressing TpoR and JAK2 V617F. It also exerted strong inhibitory effects on erythropoietin-independent erythroid colonies from MPN patients and JAK2 V617F knock-in mice, where at certain doses, a preferential inhibition of JAK2 V617F mutated progenitors was detected. Our data support the use of a combination of JAK2 and pan-class I PI3K inhibitors in the treatment of MPNs.
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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 OpenQuestion graph.