Vasculogenic mimicry of acute leukemic bone marrow stromal cells

P. Mirshahi, Arash Rafii Tabrizi, L. Vincent, A. Berthaut, R. Varin, G. Kalantar, C. Marzac, O. A. Calandini, J. P. Marie, C. Soria, J. Soria, M. Mirshahi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1039-1048
Number of pages10
JournalLeukemia
Volume23
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Mesenchymal Stromal Cells
Leukemia
Intercellular Signaling Peptides and Proteins
Insulin
Stem Cells
Bone Marrow
GTP Phosphohydrolases
Neutralizing Antibodies
Phosphatidylinositol 3-Kinases

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Mirshahi, P., Tabrizi, A. R., Vincent, L., Berthaut, A., Varin, R., Kalantar, G., ... Mirshahi, M. (2009). Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia, 23(6), 1039-1048. https://doi.org/10.1038/leu.2009.10

Vasculogenic mimicry of acute leukemic bone marrow stromal cells. / Mirshahi, P.; Tabrizi, Arash Rafii; Vincent, L.; Berthaut, A.; Varin, R.; Kalantar, G.; Marzac, C.; Calandini, O. A.; Marie, J. P.; Soria, C.; Soria, J.; Mirshahi, M.

In: Leukemia, Vol. 23, No. 6, 2009, p. 1039-1048.

Research output: Contribution to journalArticle

Mirshahi, P, Tabrizi, AR, Vincent, L, Berthaut, A, Varin, R, Kalantar, G, Marzac, C, Calandini, OA, Marie, JP, Soria, C, Soria, J & Mirshahi, M 2009, 'Vasculogenic mimicry of acute leukemic bone marrow stromal cells', Leukemia, vol. 23, no. 6, pp. 1039-1048. https://doi.org/10.1038/leu.2009.10
Mirshahi P, Tabrizi AR, Vincent L, Berthaut A, Varin R, Kalantar G et al. Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia. 2009;23(6):1039-1048. https://doi.org/10.1038/leu.2009.10
Mirshahi, P. ; Tabrizi, Arash Rafii ; Vincent, L. ; Berthaut, A. ; Varin, R. ; Kalantar, G. ; Marzac, C. ; Calandini, O. A. ; Marie, J. P. ; Soria, C. ; Soria, J. ; Mirshahi, M. / Vasculogenic mimicry of acute leukemic bone marrow stromal cells. In: Leukemia. 2009 ; Vol. 23, No. 6. pp. 1039-1048.
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