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Published on: January 24, 2020
[Research Progress on TKI Resistance of CML Cells Mediated by MSC through CXCL12/CXCR4 Axis]
Li-Jun Fang1,2, Huai-Jun Tu3, Jian Li1
1Key Laboratory of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
Abstract:
Although the tyrosinekinase inhibitors (TKI) displayed a significant curative effect on chronic myeloid leukemia (CML), but the drug resistance in treatment course of this disease still can not be avoided. Studies recently have shown that the mesenchymal stem cells (MSC) can induce CML cells to resist TKI therapy by CXCL12/CXCR4 axis from multiple aspects, such as the directional migration of CML cells, adherence to marrow cavity, the mediation of cell protective dormancy, activations of numerous survival signaling pathways, the suppression of mitochondrial-dependent apoptosis and the up-regulated expression of BCL-6. The combination of TKI and CXCR4 antagonists will be a novel treatment strategy to raise the genetic cure rate of CML. In this article, the pathways of drug resistance, pathways of sensitivity to CXCL12 and pathways of CML cell adherence to marrow cavity in CML cells mediated by MSC were reviewed.
Insights
Mesenchymal stem cells (MSC) promote chronic myeloid leukemia (CML) drug resistance via the CXCL12/CXCR4 axis. Combining TKIs with CXCR4 antagonists may overcome resistance and improve CML cure rates.
Area of Science:
- Hematology
- Cancer Biology
- Cell Biology
Context:
- Tyrosine kinase inhibitors (TKIs) are effective for chronic myeloid leukemia (CML).
- Drug resistance remains a significant challenge in CML treatment.
- Mesenchymal stem cells (MSCs) have been implicated in promoting CML drug resistance.
Purpose:
- To review the mechanisms by which MSCs induce TKI resistance in CML cells.
- To explore the role of the CXCL12/CXCR4 axis in MSC-mediated CML drug resistance.
- To discuss novel therapeutic strategies combining TKIs with CXCR4 antagonists.
Summary:
- MSCs induce CML cell resistance to TKIs through the CXCL12/CXCR4 axis.
- This involves promoting CML cell migration, marrow adherence, dormancy, survival signaling, and inhibiting apoptosis.
- BCL-6 expression is also upregulated in MSC-influenced CML cells.
Impact:
- Understanding MSC-mediated resistance pathways can lead to improved CML therapies.
- Targeting the CXCL12/CXCR4 axis offers a promising strategy to overcome TKI resistance.
- Combination therapy with TKIs and CXCR4 antagonists may enhance the genetic cure rate for CML.
