ArticleOncogene2018
Inhibition of maternal embryonic leucine zipper kinase with OTSSP167 displays potent anti-leukemic effects in chronic lymphocytic leukemia.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- TRAF1 S146 is constitutively phosphorylated in OP9-cultured primary chronic lymphocytic leukemia cells by PKN1/2.ImmunoHorizons · 2026Article
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Phosphosite-specific co-regulation networks of MELK kinase: insights from integrative global phosphoproteomes.Journal, genetic engineering & biotechnology · 2026Article
- PRMT1 facilitates the tumorigenesis of chronic lymphocytic leukemia by regulating methylation of MAST1.Leukemia · 2026Article
- Maternal Embryonic Leucine Zipper Kinase (Biology · 2026Review
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.Anti-cancer agents in medicinal chemistry · 2025Review
- ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia.Cellular & molecular biology letters · 2024Article
- Discovery of first-in-class PROTACs targeting maternal embryonic leucine zipper kinase (MELK) for the treatment of Burkitt lymphoma.RSC medicinal chemistry · 2024Article
- Article
- FOXM1 promotes TGF-β2-induced injury of human lens epithelial cells by up regulating VEGFA expression.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Article
- Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Competing endogenous RNA networks related to prognosis in chronic lymphocytic leukemia: comprehensive analyses and construction of a novel risk score model.Biomarker research · 2022Article
- MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NF‑κB pathway.International journal of oncology · 2022Article
- Targeting metabolic reprogramming in chronic lymphocytic leukemia.Experimental hematology & oncology · 2022Review
- Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer.Biochemical genetics · 2022Article
- MammaPrint and BluePrint comprehensively capture the cancer hallmarks in early-stage breast cancer patients.Genes, chromosomes & cancer · 2022Article
- Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in periodontitis.Journal of oral microbiology · 2022Article
- Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.Current research in virological science · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP53 pathway defects contributed to therapy resistance and adverse clinical outcome in chronic lymphocytic leukemia (CLL), which represents an unmet clinical need with few therapeutic options. Maternal embryonic leucine zipper kinase (MELK) is a novel oncogene, which plays crucial roles in mitotic progression and stem cell maintenance. OTSSP167, an orally administrated inhibitor targeting MELK, is currently in a phase I/II clinical trial in patients with advanced breast cancer and acute myeloid leukemia. Yet, no investigation has been elucidated to date regarding the oncogenic role of MELK and effects of OTSSP167 in chronic lymphocytic leukemia (CLL). Previous studies confirmed MELK inhibition abrogated cancer cell survival via p53 signaling pathway. Thus, we aimed to determine the biological function of MELK and therapeutic potential of OTSSP167 in CLL. Herein, MELK over-expression was observed in CLL cells, and correlated with higher WBC count, advanced stage, elevated LDH, increased β2-MG level, unmutated IGHV, positive ZAP-70, deletion of 17p13 and inferior prognosis of CLL patients. In accordance with functional enrichment analyses in gene expression profiling, CLL cells with depletion or inhibition of MELK exhibited impaired cell proliferation, enhanced fast-onset apoptosis, induced G2/M arrest, attenuated cell chemotaxis and promoted sensitivity to fludarabine and ibrutinib. However, gain-of-function assay showed increased cell proliferation and cell chemotaxis. In addition, OTSSP167 treatment reduced phosphorylation of AKT and ERK1/2. It decreased FoxM1 phosphorylation, expression of FoxM1, cyclin B1 and CDK1, while up-regulating p53 and p21 expression. Taken together, MELK served as a candidate of therapeutic target in CLL. OTSSP167 exhibits potent anti-tumor activities in CLL cells, highlighting a novel molecule-based strategy for leukemic interventions.
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