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Acute Leukemias

Functional integration of acute myeloid leukemia into the vascular niche

Leukemia volume 28, pages 1978–1987 (2014)Cite this article

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Abstract

Vascular endothelial cells are a critical component of the hematopoietic microenvironment that regulates blood cell production. Recent studies suggest the existence of functional cross-talk between hematologic malignancies and vascular endothelium. Here we show that human acute myeloid leukemia (AML) localizes to the vasculature in both patients and in a xenograft model. A significant number of vascular tissue-associated AML cells (V-AML) integrate into vasculature in vivo and can fuse with endothelial cells. V-AML cells acquire several endothelial cell-like characteristics, including the upregulation of CD105, a receptor associated with activated endothelium. Remarkably, endothelial-integrated V-AML shows an almost fourfold reduction in proliferative activity compared with non-vascular-associated AML. Primary AML cells can be induced to downregulate the expression of their hematopoietic markers in vitro and differentiate into phenotypically and functionally defined endothelial-like cells. After transplantation, these leukemia-derived endothelial cells are capable of giving rise to AML. These novel functional interactions between AML cells and normal endothelium along with the reversible endothelial cell potential of AML suggest that vascular endothelium may serve as a previously unrecognized reservoir for AML.

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Acknowledgements

We thank Pamela Canaday from the OHSU flow cytometry core for FACS. Funding was provided by the NIH to WHF (P30 CA069533 and R01 HL069133), CRC (K08 DK067359) and EWS (R01 HL70738). The Leukemia & Lymphoma Society also supported CRC with a Translational Research Program grant (6264-08) and a Scholar in Clinical Research award (2400-13).

Author information

Author notes

  1. G J Madlambayan

    Present address: 7Present address: Department of Biological Sciences, Oakland University, Rochester, MI, USA.,

  2. C R Cogle, D C Goldman and G J Madlambayan: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA

    C R Cogle, G J Madlambayan, A Meacham & R A Hromas

  2. Department of Pediatrics, Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Sciences University, Portland, OR, USA

    D C Goldman, R P Leon, A Al Masri, H A Clark, S A Asbaghi, T Kovacsovics, Q Liu, K L Hamlin & W H Fleming

  3. Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Sciences University, Portland, OR, USA

    D C Goldman, R P Leon, A Al Masri, H A Clark, S A Asbaghi, J W Tyner, J Dunlap, G Fan, T Kovacsovics, Q Liu, K L Hamlin & W H Fleming

  4. Department of Pathology, Oregon Health & Sciences University, Portland, OR, USA

    J Dunlap & G Fan

  5. Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA

    E W Scott

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Correspondence to W H Fleming.

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Cogle, C., Goldman, D., Madlambayan, G. et al. Functional integration of acute myeloid leukemia into the vascular niche. Leukemia 28, 1978–1987 (2014). https://doi.org/10.1038/leu.2014.109

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