Retrovirus-transformed erythroleukemia cells induce central nervous system failure in a new syngeneic mouse model of meningeal leukemia

Macpherson, Gordon R.; Hanson, Charlotte A.; Thompson, Delores M.; Perella, Christine M.; Cmarik, Joan L.; Ruscetti, Sandra K.

doi:10.1016/j.leukres.2011.08.019

« Previous Next »Leukemia Research
Volume 36, Issue 3 , Pages 369-376, March 2012

Retrovirus-transformed erythroleukemia cells induce central nervous system failure in a new syngeneic mouse model of meningeal leukemia

Gordon R. Macpherson
- Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, USA
Charlotte A. Hanson
- Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, USA
Delores M. Thompson
- Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, USA
Christine M. Perella
- Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, MD, USA
Joan L. Cmarik
- Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, USA
Sandra K. Ruscetti
- Laboratory of Cancer Prevention, National Cancer Institute-Frederick, Frederick, MD, USA
- Corresponding author at: Laboratory of Cancer Prevention, National Cancer Institute-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA. Tel.: +1 301 846 5740; fax: +1 301 846 6164.

Received 24 June 2011; received in revised form 15 August 2011; accepted 22 August 2011. published online 19 September 2011.

Abstract

Lack of suitable mouse models for central nervous system (CNS)-associated leukemias has hindered mechanism-guided development of therapeutics. By transplanting retrovirus-transformed mouse erythroleukemia cells into syngeneic mice, we developed a new animal model of meningeal leukemia associated with rapid paralysis. Necropsy revealed massive proliferation of the leukemic cells in the bone marrow (BM) followed by pathological angiogenesis and invasion of the leukemic cells into the meninges of the CNS. Further analysis demonstrated that the erythroleukemia cells secreted high levels of VEGF and preferentially adhered in vitro to fibronectin. This unique animal model for meningeal leukemia should facilitate studies of engraftment and proliferation of leukemic cells in the BM and their invasion of the CNS as well as pre-clinical evaluation of experimental therapeutics for CNS-associated leukemias.

Keywords: Animal model, Meningeal leukemia, Murine erythroleukemia cells, Cell adhesion, Angiogenesis, PU.1, Friend SFFV