title: Induction of Multidrug Resistance of Acute Myeloid Leukemia Cells by Cocultured Stromal Cells via Upregulation of the PI3K/Akt Signaling Pathway.
abstract: This study aimed to investigate the role of the PI3K/Akt signaling pathway in multidrug resistance of acute myeloid leukemia (AML) cells induced by cocultured stromal cells. Human AML cell lines HL-60 and U937 were adhesion cocultured with human bone marrow stromal cell line HS-5 cells. Such coculturing induced HL-60 and U937 cells resistant to chemotherapeutic drugs including daunorubicin (DNR), homoharringtonine (HHT), and cytosine arabinoside (Ara-C). The coculturing-induced resistance of AML cells to DNR, HHT, and Ara-C can be partially reversed by inhibition of the PI3K/Akt signaling pathway. Clinically, AML patients with a low level of PTEN and a high level of CCND1 had high relapse rates within 1 year, and newly diagnosed AML patients with extramedullary infiltration had a low level of PTEN. This study confirms the involvement of the PI3K/Akt signaling pathway in multidrug resistance in AML cells induced by stroma and suggests that the expression of PTEN and CCND1 may be a prognostic indicator for AML.
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fujian, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Jin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Peidong
authors.initials: P
authors.lastname: You
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.forename: Huifang
authors.initials: H
authors.lastname: Huang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D015415:Biomarkers; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt