Back to Search
Start Over
Mesenchymal stromal cells confer chemoresistance to myeloid leukemia blasts through Side Population functionality and ABC transporter activation
- Source :
- Haematologica
- Publication Year :
- 2019
- Publisher :
- Ferrata Storti Foundation (Haematologica), 2019.
-
Abstract
- Targeting chemoresistant malignant cells is one of the current major challenges in oncology. Therefore, it is mandatory to refine the characteristics of these cells to monitor their survival and develop adapted therapies. This is of particular interest in acute myeloid leukemia (AML), for which the 5-year survival rate only reaches 30%, regardless of the prognosis. The role of the microenvironment is increasingly reported to be a key regulator for blast survival. In this context, we demonstrate that contact with mesenchymal stromal cells promotes a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation leads to the induction of a Side Population (SP) phenotype in a subpopulation of primary leukemia blasts through alpha (α)4 engagement. The stroma-promoting effect is reversible and is observed with stromal cells isolated from either healthy donors or leukemia patients. Blasts expressing an SP phenotype are mostly quiescent and are chemoresistant in vitro and in vivo in patient-derived xenograft mouse models. At the transcriptomic level, blasts from the SP are specifically enriched in the drug metabolism program. This detoxification signature engaged in contact with mesenchymal stromal cells represents promising ways to target stroma-induced chemoresistance of AML cells.
- Subjects :
- Acute Myeloid Leukemia
Stromal cell
ATP-binding cassette transporter
Context (language use)
Biology
Article
Transcriptome
Mice
03 medical and health sciences
0302 clinical medicine
Side population
hemic and lymphatic diseases
Tumor Microenvironment
medicine
Animals
Humans
Mesenchymal stem cell
Myeloid leukemia
Mesenchymal Stem Cells
Hematology
medicine.disease
Leukemia, Myeloid, Acute
Leukemia
Drug Resistance, Neoplasm
Cancer research
ATP-Binding Cassette Transporters
Stromal Cells
030215 immunology
Subjects
Details
- ISSN :
- 15928721 and 03906078
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....8b463ab1c5bf957232b14ff9fdcd798f