title: Increased Th17 cells and IL-17A exist in patients with B cell acute lymphoblastic leukemia and promote proliferation and resistance to daunorubicin through activation of Akt signaling.
abstract: Immune regulation is crucial for the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL). It has been reported that Th17 cells as a newly identified subset of CD4(+) T cells are involved in the pathogenesis of several hematological disorders. However, the role of Th17 cells in the pathophysiology of B-ALL is still unclear.
  
  
  
  The frequencies of T cells were determined by flow cytometry in the peripheral blood and bone marrow of 44 newly diagnosed B-ALL patients and 25 age-matched healthy donors. The cell viability and apoptosis were determined by CCK-8 assay and Annexin V staining, respectively. Western blot was applied to identify the level of Akt and Stat3 phosphorylation.
  
  
  
  We assessed and observed a significantly increased frequency of Th17 cells and a drastically decreased frequency of Th1 cells in peripheral blood mononuclear cells and bone marrow mononuclear cells from newly diagnosed B-ALL patients compared with healthy donors. Furthermore, increased levels of Th17-related cytokines including IL-17, IL-21, IL-23, IL-1β, and IL-6 were presented in between blood and marrow in B-ALL patients. Both IL-17A and IL-21, two Th17-secreted cytokines, induced the proliferation of B-ALL cell line Nalm-6 and patient B-ALL cells isolated from B-ALL patients, herein either cytokine led to the phosphorylation of Akt and Stat3. Additionally, IL-17A promoted resistance to daunorubicin via activation of Akt signaling and the PI3K/Akt inhibitor LY294002 or perifosine almost completely rescued daunorubicin-induced cell death in B-ALL cells.
  
  
  
  Our findings suggest that elevated Th17 cells secrete IL-17A by which promotes the proliferation and resistance to daunorubicin in B-ALL cells through activation of Akt signaling. Th17 cells may represent a novel target to improve B-ALL immunotherapy.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors.forename: Laixi
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors.forename: Aifang
authors.initials: A
authors.lastname: Ye
authors.affiliation: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China. shenghuizhang1@126.com.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Laboratory of Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China. yxhan2001@163.com.
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D000098546:Interleukin-21; D003630:Daunorubicin
keywords: B-cell acute lymphoblastic leukemia; IL-17A; Th1 cells; Th17 cells