ArticleMolecular therapy oncolytics2020
A Novel Aurora Kinase Inhibitor Attenuates Leukemic Cell Proliferation Induced by Mesenchymal Stem Cells.
Article in Molecular therapy oncolytics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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.
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Who cites it
4 citing papers in PubMed.
- Blood Serum from Patients with Acute Leukemia Inhibits the Growth of Bone Marrow Multipotent Mesenchymal Stromal Cells.Biomedicines · 2025Article
- Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor.International journal of molecular medicine · 2022Article
- A Temporal PROTAC Cocktail-Mediated Sequential Degradation of AURKA Abrogates Acute Myeloid Leukemia Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Molecular Profiling of Kenyan Acute Myeloid Leukemia Patients.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Acute myeloid leukemia (AML) mesenchymal stem cells (MSCs) play an essential role in protecting leukemic cells from chemotherapeutic agents through activating a wide range of adhesion molecules and cytokines. Thus, more attention should be paid to attenuate the protection of leukemic cells by MSCs. By examining the gene expression files of MSCs from healthy donors and AML patients through high-throughput microarrays, we found that interleukin (IL)-6 was an important cytokine secreted by AML MSCs to protect leukemic cells, contributing to disease progression. Strikingly, Aurora A (AURKA) was activated by IL-6, offering a new target to interfere with leukemia. Importantly, a novel AURKA inhibitor, PW21, showed excellent AURKA kinase inhibitory activities and attenuated the interaction of leukemic cells and the microenvironment. PW21 inhibited MSC-induced cell proliferation, colony formation, and migration, and it induced cell apoptosis. Mechanically, PW21 could inhibit IL-6 secreted by MSCs. Moreover, we found that PW21 displayed a strong anti-leukemia effect on non-obese diabetic (NOD)-severe combined immunodeficiency (SCID) and murine MLL-AF9 leukemic models. PW21 significantly prolonged the survival of leukemic mice and eliminated the leukemic progenitor cells. AURKA inhibitor PW21 could provide a new approach for treatment of leukemia through blocking the protection by the leukemic microenvironment in clinical application.
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Registered trials
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