ArticleBlood2020
Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- Structure-Activity Relationship Studies Resulting in the Identification of Potent and Selective Salt-Inducible Kinase Inhibitors.ACS medicinal chemistry letters · 2026Article
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- TCF3::HLF orchestrates an enhancer-promoter network with activation of MEF2C to promote immature HSC gene expression in leukemia.Science advances · 2026Article
- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- MEF2C: A Novel Transcription Factor Implicated in Human Malignant Tumors.Current topics in medicinal chemistry · 2026Review
- KLF5 enables dichotomous lineage programs in pancreatic cancer via the AAA+ ATPase coactivators RUVBL1 and RUVBL2.Nature communications · 2025Article
- Advanced modeling of salt-inducible kinase (SIK) inhibitors incorporating protein flexibility through molecular dynamics and cross-docking.Scientific reports · 2025Article
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Functional characterization of alleLife · 2025Article
- Super-enhancer-associated LINC00963 promotes metastasis of gastric cancer through epithelial-mesenchymal transition.PloS one · 2025Article
- MEF2A is a transcription factor for circPVT1 and contributes to the malignancy of acute myeloid leukemia.International journal of oncology · 2024Article
- Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL).International journal of molecular sciences · 2024Article
- Targeting SIK3 to modulate hippocampal synaptic plasticity and cognitive function by regulating the transcription of HDAC4 in a mouse model of Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Narazaciclib, a novel multi-kinase inhibitor with potent activity against CSF1R, FLT3 and CDK6, shows strong anti-AML activity in defined preclinical models.Scientific reports · 2024Article
- IκBζ is a dual-use coactivator of NF-κB and POU transcription factors.Molecular cell · 2024Article
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Lineage-defining transcription factors (TFs) are compelling targets for leukemia therapy, yet they are among the most challenging proteins to modulate directly with small molecules. We previously used CRISPR screening to identify a salt-inducible kinase 3 (SIK3) requirement for the growth of acute myeloid leukemia (AML) cell lines that overexpress the lineage TF myocyte enhancer factor (MEF2C). In this context, SIK3 maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), a repressive cofactor of MEF2C. In this study, we evaluated whether inhibition of SIK3 with the tool compound YKL-05-099 can suppress MEF2C function and attenuate disease progression in animal models of AML. Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions. Similar phenotypes were obtained when cells were exposed to YKL-05-099, which caused cell-cycle arrest and apoptosis in MEF2C-expressing AML cell lines. An epigenomic analysis revealed that YKL-05-099 rapidly suppressed MEF2C function by altering the phosphorylation state and nuclear localization of HDAC4. Using a gatekeeper allele of SIK3, we found that the antiproliferative effects of YKL-05-099 occurred through on-target inhibition of SIK3 kinase activity. Based on these findings, we treated 2 different mouse models of MLL-AF9 AML with YKL-05-099, which attenuated disease progression in vivo and extended animal survival at well-tolerated doses. These findings validate SIK3 as a therapeutic target in MEF2C-addicted AML and provide a rationale for developing druglike inhibitors of SIK3 for definitive preclinical investigation and for studies in human patients.
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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.