Figure 2. FTY720 does not reduce Ph− ALL in a μodel of early disease.

(A) Groups of 6 NOD/SCIDγc^−/− μice were engrafted with the indicated human ALL xenografts. After 3 to 7 days, 10 mg/kg (1345, 1999, 2070, ALL-55 and ALL-56) or 5 mg/kg (0398) of FTY720, or 0.9% sodium chloride was administered daily by intra-peritoneal injection for three weeks. Surviving animals were sacrificed at the end of treatment and the level of leukemia analyzed by flow cytometry. The number of ALL cells ×10⁶ in the bone marrow, spleen and blood is reported with each dot representing an individual animal and the bar the mean of the cohort. #p<0.05 indicating increased disease and §p<0.05 reduced disease compared to control. (B) Increased infiltration of the liver following FTY720 treatment. Livers collected at the time of sacrifice from the animals shown in figure 1A were formalin fixed and paraffin embedded. Sections were stained with hematoxylin and eosin and examined by light microscopy. Representative control and FTY720-treated sections are shown for xenografts 1345 and 1999. Xenografts 0398 and 2070 had minimal leukemia in the liver. (C) Total ALL burden was calculated for each animal from the numbers of ALL cells in each compartment (peripheral blood, bone marrow and spleen). The number of ALL cells ×10⁹ is reported with each dot representing an individual animal and the bar the mean of the cohort. #p<0.05 indicating increased disease and §p<0.05 reduced disease compared to control.