Hyaluronan abrogates imatinib-induced senescence in chronic myeloid leukemia cell lines
Open accessAbstract
Hyaluronan (HA) is the main glycosaminoglycan of the extracellular matrix. CD44 is the most important HA receptor, and both have been associated with poor prognosis in cancer. Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively activated tyrosine kinase (Breakpoint Cluster Region - Abelson murine leukemia viral oncogene homolog1, BCR-ABL). It is mainly treated with BCR-ABL inhibitors, such as imatinib. However, the selection of resistant cells leads to treatment failure. The aim of this work was to determine the capacity of HA (high molecular weight) to counteract the effect of imatinib in human CML cell lines (K562 and Kv562). We demonstrated that imatinib decreased HA levels and the surface expression of CD44 in both cell lines. Furthermore, HA abrogated the anti-proliferative and pro-senescent effect of Imatinib without modifying the imatinib-induced apoptosis. Moreover, the inhibition of HA synthesis with 4-methylumbelliferone enhanced the anti-proliferative effect of imatinib. These results suggest that Imatinib-induced senescence would depend on the reduction in HA levels, describing, for the first time, the role of HA in the development of resistance to imatinib. These findings show that low levels of HA are crucial for an effective therapy with imatinib in CML.
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K562 is difficult to become senescent, despite being senescence-inducible by certain therapies such as imatinib.
“K562, the p53-deficient cancer cell line, is difficult to become senescent, despite senescence-inducible by certain therapies, such as imatinib.122,123”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [123]
The Results section ('HA prevents imatinib-induced senescence'; page unavailable) reports that imatinib increased senescence markers in K562 cells. The cited paper does not establish that K562 is generally difficult to make senescent or describe it as p53-deficient. (LLM, conf=0.85)
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- Authors
- Lompardía, S., Díaz, M., Pibuel, M., Papademetrio, D., Poodts, D., Mihalez, C., Álvarez, É., & Hajos, S.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Universidad de Buenos Aires (AR)
- Corresponding author
- Lompardía, Silvina
- Venue
- Scientific Reports
- Published
- 2019-07-29
- Volume
- 9
- Issue
- 1
- Pages
- 10930-10930
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6662747
- OpenAlex
- W2966198309
- Cited by
- 19
- References
- 58
- Citations by year
- 2026: 3 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-07-16)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Greater South Information System
- Funders
- Universidad de Buenos Aires (UBACYT 20020130100415BA)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- hyaluronic acid, imatinib, chronic myeloid leukemia, cellular senescence, CD44, BCR-ABL, imatinib resistance, 4-methylumbelliferone, hyaluronan synthesis inhibition, K562 cells, extracellular matrix, glycosaminoglycans, apoptosis
- MeSH terms
- Imatinib Mesylate, Antineoplastic Agents, Humans, Hyaluronic Acid, Hymecromone, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Fusion Proteins, bcr-abl, Cellular Senescence, Apoptosis, Hyaluronan Receptors, Drug Resistance, Neoplasm, Cell Line, Tumor, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Proto-Oncogene Proteins c-akt
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