Hypothetical model of the influence of VEGF on BCR signaling in 3 scenarios: (I) Lack of adequate VEGF stimulation leads to low PKCbeta expression and insufficient survival signals along the BCR signaling pathway. (III) A too strong PKCbeta signal may lead to excess negative feedback via Btk and again negatively impact on the critical ratio of prosurvival and death signals likely converging in the Bcl2 family. Only an optimal BCR signaling strength may be able to support CLL survival (II) and VEGF may be an important determinant of the fine tuning.