title: Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD.
abstract: OBJECTIVE
  Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML.
  
  
  METHODS
  Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2.
  
  
  RESULTS
  VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component.
  
  
  CONCLUSIONS
  Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.
authors.affiliation: Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kupsa
authors.affiliation: Department of Informatics and Quantitative Methods, , Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Vanek
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Vasatova
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Karesova
authors.affiliation: 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Zak
authors.affiliation: Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Jebavy
authors.affiliation: Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Horacek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3 / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: FLT3-ITD; TNF-alpha; acute myeloid leukemia; adhesion molecules; cytokines