Circulating and local VEGF/P1GF levels correlate with ALL progression. (A) FLT-1 neutralization reduces the levels of circulating human VEGF plasma levels in NOD-SCID mice inoculated with 697 ALL cells. Results show a significant decrease (P < .05) in human VEGF levels (ELISA) in the plasma of NOD-SCID mice inoculated with the 697 cell line (after 10 days) and treated every other day with the FLT-1-neutralizing Ab 6.12 (FLT-1 Ab, 500 ng/injection). These results were obtained in 3 independent experiments. (B) VEGF and PlGF accumulate in the epiphysis of long bones of normal (nonleukemic) NOD-SCID mice, littermate controls of mice used in all the other experiments described in this paper. Images (at × 200 magnification) show BM sections, localized to the diaphysis or epiphysis, stained with mVEGF- and mPlGF-specific Abs. Note the clear accumulation of VEGF and PlGF (brown staining) close to the epiphyseal regions of the bone, whereas the diaphysis shows little evidence for VEGF or PlGF staining. Results shown were obtained from 2 independent determinations, done in animals of different ages. Error bars indicate standard deviation. Image acquisition performed as for Figure 3.