title: Osteoblasts increase proliferation and release of pro-angiogenic interleukin 8 by native human acute myelogenous leukemia blasts.
abstract: OBJECTIVE
  Interactions between acute myelogenous leukemia (AML) blasts and non-leukemic cells in the bone marrow seem to be important for both disease development and susceptibility to chemotherapy. Recent studies have focused on the endothelial cells, but other non-leukemic cells may also be involved. In the present study we investigated how osteoblasts affect native human AML blasts.
  
  
  METHODS
  AML cells were derived from a large group of consecutive patients. The AML blasts and osteoblastic sarcoma cell lines (Cal72, SJSA-1) were incubated together in different chambers separated by a semipermeable membrane. We investigated effects of co-culture on proliferation, apoptosis and cytokine release.
  
  
  RESULTS
  The cross-talk between these two cell populations, achieved via release of soluble mediators, resulted in increased AML blast proliferation, including increased proliferation of clonogenic progenitors, but did not affect spontaneous in vitro apoptosis. Both interleukin (IL) 1-b and granulocyte-macrophage colony-stimulating factor were involved in this growth-enhancing cross-talk, and normal osteoblasts could also increase the AML blast proliferation. Furthermore, co-culture of AML blasts with osteoblastic sarcoma cells as well as normal osteoblasts increased the levels of the pro-angiogenic mediator IL8.
  
  
  CONCLUSIONS
  Our in vitro results suggest that the release of soluble mediators by osteoblasts supports leukemic hematopoiesis through two major mechanisms: (i) direct enhancement of AML blast proliferation; and (ii) enhanced angiogenesis caused by increased IL8 levels.
authors.affiliation: Division for Hematology, Department of Medicine, Haukeland University Hospital and The University of Bergen, Bergen, Norway. oystein.bruserud@haukeland.no
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
authors.forename: Anita
authors.initials: A
authors.lastname: Ryningen
authors.forename: Line
authors.initials: L
authors.lastname: Wergeland
authors.forename: Nils Idar
authors.initials: NI
authors.lastname: Glenjen
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D017209:Apoptosis; D002450:Cell Communication; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010006:Osteoblasts / Q000166:cytology*; D012516:Osteosarcoma / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D016209:Interleukin-8