Osteoblasts increase proliferation and release of pro-angiogenic interleukin 8 by native human acute myelogenous leukemia blasts.
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.
Bruserud
Øystein
Ø
Division for Hematology, Department of Medicine, Haukeland University Hospital and The University of Bergen, Bergen, Norway. oystein.bruserud@haukeland.no
Ryningen
Anita
A
Wergeland
Line
L
Glenjen
Nils Idar
NI
Gjertsen
Bjørn Tore
BT
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
D016207:Cytokines; D016209:Interleukin-8