A novel bone biopsy technique was used to generate a robust stromal cell system to study how stroma modulates CLL B-cell apoptosis and how the leukemic cell-stromal interaction influences secretion of vascular factors. Marrow stromal elements (MSE) rescued CLL B-cells from both spontaneous and drug induced apoptosis, partly due to soluble factors. When CLL B-cells were added to the MSE cultures, a dramatic increase in the secretion of basic fibroblast growth factor and decrease in the secretion of thrombospondin was observed. These results indicate the interaction between CLL B-cells and marrow stromal elements regulates angiogenic switching and may be linked to disease progression.