Research Highlights

Nature Reports Stem Cells
Published online: 1 November 2007 | doi:10.1038/stemcells.2007.112

Leukemia might elbow out blood makers

Monya Baker¹

A new mouse model helps researchers study human cancer cells

A multi-immunodeficient mouse model mouse has proved itself a new, powerful tool for studying acute myelogenous leukemia (AML), the most common form of adult leukemia¹. Starting with cells collected from human patients, the mouse allowed leukemia stem cells to be passed from one mouse to another through blood transfers of just 100 to 1,000 carefully selected blood cells, showing that rare leukemia stem cells can renew the disease. Studies also revealed where the leukemia cells go once released in the blood: they home to the inner surface of bones, where they are better able to resist a common chemotherapeutic.

Though researchers have long used mice to study leukemia, they've encountered obstacles to using human cancer cells. Mice designed not to reject human cells tend not to live very long, and sometimes the immune system asserts itself and attacks foreign cells. To create a better way to study AML, a kind of leukemia associated with old age, Fumihiko Ishikawa at the RIKEN Research Unit for Human Disease Models in Yokohama and colleagues created a longer-lived mouse model (in the terms of the trade, NOD/SCID/IL2^null) less likely to reject human cells. Unlike other models, this one allows efficient, long-term engraftment of leukemia stem cells.

As in humans, the more leukemia cells the mice had, the less able they were to make red blood cells and platelets. A search for these human cells within the mice suggested a reason why. Once injected intravenously, human leukemia cells find their way inside bones and engraft in a particular part of bone marrow, the endosteal surface. This happens to be the very same place where red blood cells are made, suggesting that leukemia stem cells compete with blood-forming stem cells for their niche.

This insight is not the only one to come from this new mouse model, however. Treatment of the mice with a common anti-leukemia agent, cytosine arabinoside, showed that leukemia stem cells at the endosteal surface, but not elsewhere, were relatively protected from drug-induced apoptosis.

Studies examining the expression of many genes (global transcription profiling) showed that even when the leukemia stem cells were transplanted through a series of mice, the activity of expected genes stayed constant. In addition to testing new therapeutics, researchers should be able to use this mouse model to generate large numbers of leukemia cells from a given patient and so better study the cells. This could help dissect drug resistance mechanisms within individual patients and identify new ways to attack the disease.

Author affiliation

1. Monya Baker is news editor of Nature Reports Stem Cells