title: Elevated markers of inflammation and endothelial activation and increased counts of intermediate monocytes in adult survivors of childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Adult survivors of childhood malignancy are prone to accelerated atherogenesis and late cardiovascular complications. Plaque formation is initiated by recruitment of monocytes and T-cells into the intima, mediated by adhesion molecules and chemokines expressed by activated endothelial cells.
  
  
  OBJECTIVE
  To assess markers of inflammatory activity, endothelial activation as well as monocyte heterogeneity in adult survivors of childhood acute lymphoblastic leukemia (ALL) who had been treated with chemotherapy without cranial irradiation.
  
  
  RESULTS
  We studied 27 (age: 18-28 years) healthy survivors of childhood ALL and 20 controls (age: 20-31 years). Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+) and nonclassical CD14(+)CD16(++) monocytes which were further characterized by their expression of HLA-DR and β2-integrins CD11b/CD18 and CD11c/CD18. In ALL survivors we found increased levels of pentraxin-3 (median [interquartile range]: 0.63 [0.36-0.94] vs. 0.40 [0.32-0.57] ng/ml; p = 0.03), soluble vascular cell adhesion molecule-1 (687 [597-761] vs. 558 [534-702]ng/ml; p = 0.02), osteoprotegerin (mean ± SD: 5.24 ± 1.00 vs. 4.42 ± 1.34 pmol/l; p = 0.02) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (107.0 ± 23.6 vs. 89.5 ± 18.9 pg/ml; p = 0.01), whereas C-reactive protein, interleukin 6 and 18, TNF-α, monocyte chemotactic protein-1 and soluble intercellular adhesion molecule-1 were unchanged. Former ALL patients exhibited elevated counts of intermediate monocytes (6.3 ± 4.0 vs. 4.3 ± 1.5% of blood monocytes; p = 0.03). CD11b/CD18 and CD11c/CD18 expression on intermediate monocytes tended to be higher in ALL survivors (1917 ± 993 vs. 1396 ± 673 MFI [median fluorescence intensity]; p = 0.06 and 3883 ± 1445 vs. 3185 ± 645 MFI; p = 0.05, respectively).
  
  
  CONCLUSIONS
  Our findings suggest chronic inflammatory activation and immune dysregulation in adult survivors of childhood ALL, which can translate into late cardiovascular morbidity.
authors.affiliation: Department of Internal Medicine and Gerontology, Jagiellonian University/University Hospital, Cracow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sulicka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Surdacki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mikołajczyk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Strach
authors.forename: Barbara
authors.initials: B
authors.lastname: Gryglewska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ćwiklińska
authors.forename: Walentyna
authors.initials: W
authors.lastname: Balwierz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Guzik
authors.forename: Tomasz K
authors.initials: TK
authors.lastname: Grodzicki
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D015415:Biomarkers; D018821:CD18 Antigens; D006684:HLA-DR Antigens