ArticleThe Journal of clinical investigation2014
Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- Phase II Trial of MEK Inhibitor Binimetinib (MEK162) in RAS-mutant Acute Myeloid Leukemia.Clinical lymphoma, myeloma & leukemia · 2019Trial
- Article
- The m6A methyltransferase METTL14 promotes oncogenic Kras induced juvenile myelomonocytic leukemia through dysregulating autophagy.Cell death and differentiation · 2026Article
- Article
- A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice.The Journal of clinical investigation · 2023Article
- MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.Neuro-oncology · 2022Review
- Epigenetic downregulation of Socs2 contributes to mutant N-Ras-mediated hematopoietic dysregulation.Disease models & mechanisms · 2022Article
- Effects ofFrontiers in cell and developmental biology · 2022Article
- Article
- Article
- RAS/CBL mutations predict resistance to JAK inhibitors in myelofibrosis and are associated with poor prognostic features.Blood advances · 2020Article
- Downregulating Notch counteracts KrasLeukemia · 2019Article
- Blockade of PDGFRβ circumvents resistance to MEK-JAK inhibition via intratumoral CD8Journal of experimental & clinical cancer research : CR · 2019Article
- Unique dependence on Sos1 inBlood · 2018Article
- [Advances in the treatment of juvenile myelomonocytic leukemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Review
- Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Novel Therapies for Myelofibrosis.Current hematologic malignancy reports · 2017Review
- JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation.Journal of veterinary internal medicine · 2017Article
- Turning the tide in myelodysplastic/myeloproliferative neoplasms.Nature reviews. Cancer · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Overactive RAS signaling is prevalent in juvenile myelomonocytic leukemia (JMML) and the myeloproliferative variant of chronic myelomonocytic leukemia (MP-CMML) in humans, and both are refractory to conventional chemotherapy. Conditional activation of a constitutively active oncogenic Nras (NrasG12D/G12D) in murine hematopoietic cells promotes an acute myeloproliferative neoplasm (MPN) that recapitulates many features of JMML and MP-CMML. We found that NrasG12D/G12D-expressing HSCs, which serve as JMML/MP-CMML-initiating cells, show strong hyperactivation of ERK1/2, promoting hyperproliferation and depletion of HSCs and expansion of downstream progenitors. Inhibition of the MEK pathway alone prolonged the presence of NrasG12D/G12D-expressing HSCs but failed to restore their proper function. Consequently, approximately 60% of NrasG12D/G12D mice treated with MEK inhibitor alone died within 20 weeks, and the remaining animals continued to display JMML/MP-CMML-like phenotypes. In contrast, combined inhibition of MEK and JAK/STAT signaling, which is commonly hyperactivated in human and mouse CMML, potently inhibited human and mouse CMML cell growth in vitro, rescued mutant NrasG12D/G12D-expressing HSC function in vivo, and promoted long-term survival without evident disease manifestation in NrasG12D/G12D animals. These results provide a strong rationale for further exploration of combined targeting of MEK/ERK and JAK/STAT in treating patients with JMML and MP-CMML.
Indexed as
Identifiers
What OpenQuestion holds
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.