Affiliation:
1. The First Clinical Medical College Lanzhou University Lanzhou China
2. Central Laboratory, The First Affiliated Hospital Lanzhou University Lanzhou China
3. Gansu Key Laboratory of Genetic Study of Hematopathy Lanzhou China
Abstract
AbstractAcute myeloid leukemia (AML) has a high rate of treatment failure due to increased prevalence of therapy resistance. Mesenchymal stem cells (MSCs) in the leukemia microenvironment contribute to chemoresistance in AML, but the specific mechanism remains unclear. The critical role of the epithelial–mesenchymal transition (EMT)‐like profile in AML chemoresistance has been gradually recognized. However, there is no research to suggest that the AML‐derived bone marrow mesenchymal stem cells (AML‐MSCs) induce the EMT program in AML thus far. We isolated AML‐MSCs and cocultured them with AML cells. We found that AML‐MSCs induced a significant mesenchymal‐like morphology in drug‐resistant AML cells, but it was scarce in parental AML cells. The AML‐MSCs promoted growth of AML cells in the presence or absence of chemotherapeutics in vitro and in vivo. Acute myeloid leukemia MSCs also induced EMT marker expression in AML cells, especially in chemoresistant AML cells. Mechanistically, AML‐MSCs secreted abundant interleukin‐6 (IL‐6) and upregulated IL‐6 expression in AML cells. Acute myeloid leukemia cells upregulated IL‐6 expression in AML‐MSCs in turn. Meanwhile, AML‐MSCs activated the JAK2/STAT3 pathway in AML cells. Two JAK/STAT pathway inhibitors counteracted the AML‐MSCs induced morphology change and EMT marker expression in AML cells. In conclusion, AML‐MSCs not only promote the emergence of chemoresistance but also enhance it once AML acquires chemoresistance. AML‐MSCs induce EMT‐like features in AML cells; this phenotypic change could be related to chemoresistance progression. AML‐MSCs induce the EMT‐like program in AML cells through IL‐6/JAK2/STAT3 signaling, which provides a therapeutic target to reverse chemoresistance in AML.
Subject
Cancer Research,Oncology,General Medicine
Cited by
1 articles.
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