CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance

Lauren A. Pitt, Anastasia N. Tikhonova, Hai Hu, Thomas Trimarchi, Bryan King, Yixiao Gong, Marta Sanchez-Martin, Aris Tsirigos, Dan R. Littman, Adolfo A. Ferrando, Sean J. Morrison, David R. Fooksman, Iannis Aifantis, Susan R. Schwab

Research output: Contribution to journalArticle

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Abstract

The role of the microenvironment in Tcell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL. Moreover, genetic targeting of Cxcr4 in murine T-ALL after disease onset led to rapid, sustained disease remission, and CXCR4 antagonism suppressed human T-ALL in primary xenografts. Loss of CXCR4 targeted key T-ALL regulators, including the MYC pathway, and decreased leukemia initiating cell activity invivo. Our data identify a T-ALL niche and suggest targeting CXCL12/CXCR4 signaling as a powerful therapeutic approach for T-ALL.

Original languageEnglish (US)
Pages (from-to)755-768
Number of pages14
JournalCancer Cell
Volume27
Issue number6
DOIs
StatePublished - Jun 8 2015

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Blood Vessels
Maintenance
Leukemia
Heterografts
Bone Marrow

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Pitt, L. A., Tikhonova, A. N., Hu, H., Trimarchi, T., King, B., Gong, Y., ... Schwab, S. R. (2015). CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. Cancer Cell, 27(6), 755-768. https://doi.org/10.1016/j.ccell.2015.05.002

CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. / Pitt, Lauren A.; Tikhonova, Anastasia N.; Hu, Hai; Trimarchi, Thomas; King, Bryan; Gong, Yixiao; Sanchez-Martin, Marta; Tsirigos, Aris; Littman, Dan R.; Ferrando, Adolfo A.; Morrison, Sean J.; Fooksman, David R.; Aifantis, Iannis; Schwab, Susan R.

In: Cancer Cell, Vol. 27, No. 6, 08.06.2015, p. 755-768.

Research output: Contribution to journalArticle

Pitt, LA, Tikhonova, AN, Hu, H, Trimarchi, T, King, B, Gong, Y, Sanchez-Martin, M, Tsirigos, A, Littman, DR, Ferrando, AA, Morrison, SJ, Fooksman, DR, Aifantis, I & Schwab, SR 2015, 'CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance', Cancer Cell, vol. 27, no. 6, pp. 755-768. https://doi.org/10.1016/j.ccell.2015.05.002
Pitt LA, Tikhonova AN, Hu H, Trimarchi T, King B, Gong Y et al. CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. Cancer Cell. 2015 Jun 8;27(6):755-768. https://doi.org/10.1016/j.ccell.2015.05.002
Pitt, Lauren A. ; Tikhonova, Anastasia N. ; Hu, Hai ; Trimarchi, Thomas ; King, Bryan ; Gong, Yixiao ; Sanchez-Martin, Marta ; Tsirigos, Aris ; Littman, Dan R. ; Ferrando, Adolfo A. ; Morrison, Sean J. ; Fooksman, David R. ; Aifantis, Iannis ; Schwab, Susan R. / CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. In: Cancer Cell. 2015 ; Vol. 27, No. 6. pp. 755-768.
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