Bone marrow stromal cells induce an ALDH+ stem cell-like phenotype and enhance therapy resistance in AML through a TGF-β-p38-ALDH2 pathway

• Published in: PloS one Vol. 15; no. 11; p. e0242809
• Main Authors: Yuan, Bin, El Dana, Fouad, Ly, Stanley, Yan, Yuanqing, Ruvolo, Vivian, Shpall, Elizabeth J., Konopleva, Marina, Andreeff, Michael, Battula, Venkata Lokesh
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.11.2020; Public Library of Science (PLoS)
• Subjects: Acute myeloid leukemia; Aldehyde dehydrogenase; Aldehyde Dehydrogenase - genetics; Aldehydes; Antibodies; Biology and life sciences; Bone marrow; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Chemoresistance; Chemotherapy; Coculture Techniques; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene sequencing; Genotype & phenotype; Growth factors; HEK293 Cells; Hematology; Humans; Isoforms; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Leukemogenesis; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - pathology; Mesenchyme; Myeloid leukemia; Oxidoreductases Acting on CH-NH Group Donors - genetics; p38 Mitogen-Activated Protein Kinases - genetics; Patients; Phenotypes; Proteins; Ribonucleic acid; RNA; Signal Transduction - drug effects; Stem cells; Stromal cells; Transcription factors; Transforming Growth Factor beta1 - genetics; Transforming growth factor-b1; Tumor Microenvironment - genetics; Canada; United States > US; Texas

The bone marrow microenvironment (BME) in acute myeloid leukemia (AML) consists of various cell types that support the growth of AML cells and protect them from chemotherapy. Mesenchymal stromal cells (MSCs) in the BME have been shown to contribute immensely to leukemogenesis and chemotherapy resist...