Acute myeloid leukemia (AML)‐derived mesenchymal stem cells induce chemoresistance and epithelial–mesenchymal transition‐like program in AML through IL‐6/JAK2/STAT3 signaling

• DOI: 10.1111/cas.15855
• Publication Date: 2023-06-06T22:11:14Z
• Authors: Jianle Lu; Qiaomei Dong; Shuling Zhang; Youfan Feng; Jincai Yang; Li Zhao
• Keywords: STAT3 Transcription Factor; Epithelial-Mesenchymal Transition; Interleukin-6; Mesenchymal Stem Cells; Janus Kinase 2; 3. Good health; STAT Transcription Factors; Leukemia, Myeloid, Acute; Drug Resistance, Neoplasm; Tumor Microenvironment; Humans; ORIGINAL ARTICLES; Signal Transduction; Janus Kinases

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