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- Title
Vasculogenic mimicry of acute leukemic bone marrow stromal cells.
- Authors
Mirshahi, P.; Rafii, A.; Vincent, L.; Berthaut, A.; Varin, R.; Kalantar, G.; Marzac, C.; Calandini, O. A.; Marie, J.-P.; Soria, C.; Soria, J.; Mirshahi, M.
- Abstract
Angiogenesis is thought to be involved in the development of acute leukemia (AL). We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells might be responsible for the increase in microvascular density (MVD), and compared 13 bone marrow samples from AL patients with 23 samples from patients in complete remission (controls). We demonstrated that AL-derived BMSC secreted more insulin growth factor-1 (IGF-1) and SDF-1α than controls. In addition, in contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem cells from AL patients were able to form capillary-like structures (‘vasculogenic mimicry’) on Matrigel. The increase in vasculogenic mimicry occurred through PI3 kinase and ρ GTPase pathway as inhibitors of these signaling pathways (wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary tube formation. In normal BMSC, addition of exogenous IGF-1 generated capillary-like tubes through the same pathway as observed spontaneously in AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional abnormalities that may explain the increase in MVD in the bone marrow of AL patients.Leukemia (2009) 23, 1039–1048; doi:10.1038/leu.2009.10; published online 2 April 2009
- Subjects
NEOVASCULARIZATION; BLOOD-vessel development; ACUTE leukemia; BONE marrow; CELLULAR immunity
- Publication
Leukemia (08876924), 2009, Vol 23, Issue 6, p1039
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2009.10