Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity
Abstract
:1. Introduction
2. Results
2.1. Increased Susceptibility to MTX and VNC with Inhibitors of Stromal PKC
2.2. NF-κB and Akt Signalling Are Increased in MSC after the Co-Culture with B-ALL Cells
2.3. Blocking of NF-κB, but Not Akt, Inhibited Adhesion of B-ALL Cells to MSC without Increasing Susceptibility to DEXA or VNC
2.4. Increased Sensitization to Drug Treatment Could also Be Dissociated from NF-κB and Akt Signalling
2.5. Evaluation of Other Kinases That Could Be Involved in Drug Protection
2.6. B-ALL ABC Transporters Are Indirectly Affected by the MSC Support
3. Discussion
4. Materials and Methods
4.1. B-ALL Cell Samples and MSC Isolation and Characterization
4.2. Inhibitors of Signalling Molecules Used
4.3. Cell Adhesion Assays
4.4. Phosphorylation Evaluation by Flow Cytometry
4.5. ABC Transporters Activity
4.6. Phospho Kinase Activity and NF-κB Pathway
4.7. Drug Sensitivity in B-ALL Cells
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Ruiz-Aparicio, P.F.; Uribe, G.I.; Linares-Ballesteros, A.; Vernot, J.-P. Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity. Molecules 2021, 26, 5366. https://doi.org/10.3390/molecules26175366
Ruiz-Aparicio PF, Uribe GI, Linares-Ballesteros A, Vernot J-P. Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity. Molecules. 2021; 26(17):5366. https://doi.org/10.3390/molecules26175366
Chicago/Turabian StyleRuiz-Aparicio, Paola Fernanda, Gloria Inés Uribe, Adriana Linares-Ballesteros, and Jean-Paul Vernot. 2021. "Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity" Molecules 26, no. 17: 5366. https://doi.org/10.3390/molecules26175366