ArticleLeukemia2022
RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Non-genetic remodeling drives leukemia propagation and reveals actionable vulnerabilities in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- A structure-based modeling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemia.iScience · 2026Article
- Mitochondrial ribosomal protein L3 (MRPL3): An early diagnostic biomarker and potential molecular target in pancreatic cancer.Translational oncology · 2025Article
- Article
- Activity of trametinib as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory RAS pathway-mutated hematologic malignancies.Annals of hematology · 2025Article
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.Annals of hematology · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- Glucose Metabolism as a Potential Therapeutic Target in Cytarabine-Resistant Acute Myeloid Leukemia.Pharmaceutics · 2024Article
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- Very short insertions in the FLT3 gene are of therapeutic significance in acute myeloid leukemia.Blood advances · 2023Article
- The Contribution of Oxidative Stress toAntioxidants (Basel, Switzerland) · 2023Review
- Article
- Analysis ofTranslational pediatrics · 2023Article
- The oncogenic potential of Rab-like protein 1A (RBEL1A) GTPase: The first review of RBEL1A research with future research directions and challenges.Journal of Cancer · 2023Review
- Implications of RAS mutational status in subsets of patients with newly diagnosed acute myeloid leukemia across therapy subtypes.American journal of hematology · 2022Article
- Combination of RSK inhibitor LJH-685 and FLT3 inhibitor FF-10101 promoted apoptosis and proliferation inhibition of AML cell lines.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Functions and clinical significance of circular RNAs in acute myeloid leukemia.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
41 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent advances in acute myeloid leukemia (AML) molecular characterization and targeted therapies, a majority of AML cases still lack therapeutically actionable targets. In 127 AML cases with unmet therapeutic needs, as defined by the exclusion of ELN favorable cases and of FLT3-ITD mutations, we identified 51 (40%) cases with alterations in RAS pathway genes (RAS+, mostly NF1, NRAS, KRAS, and PTPN11 genes). In 79 homogeneously treated AML patients from this cohort, RAS+ status were associated with higher white blood cell count, higher LDH, and reduced survival. In AML models of oncogenic addiction to RAS-MEK signaling, the MEK inhibitor trametinib demonstrated antileukemic activity in vitro and in vivo. However, the efficacy of trametinib was heterogeneous in ex vivo cultures of primary RAS+ AML patient specimens. From repurposing drug screens in RAS-activated AML cells, we identified pyrvinium pamoate, an anti-helminthic agent efficiently inhibiting the growth of RAS+ primary AML cells ex vivo, preferentially in trametinib-resistant PTPN11- or KRAS-mutated samples. Metabolic and genetic complementarity between trametinib and pyrvinium pamoate translated into anti-AML synergy in vitro. Moreover, this combination inhibited the propagation of RA+ AML cells in vivo in mice, indicating a potential for future clinical development of this strategy in AML.
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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.