The WNT signaling pathway regulates many different cellular processes, among them lymphopoiesis. Especially its influence on B cell maturation is not well understood, but it is clear that abnormal pathway activity is one of the hallmarks of B cell neoplasia like chronic lymphocytic leukemia (CLL). As one of the downstream effectors of the WNT signaling cascade, LEF1 (Lymphoid enhancer-binding factor 1) was suggested to play a pivotal role in B maturation as well as in the development and in sustaining of neoplasia like CLL. The goal of this project was to develop an easily adaptable LEF1 dependent mouse model to elucidate the effects of LEF1 overexpression in B cells and other tissues. Furthermore, it was designed to test whether the LEF1 overexpression, which is common in several cancers, has oncogenic potential. The secondary goal of this project is to test if newly developed NO-ASA derivates, a known class of WNT inhibitors, might provide a feasible strategy for experimental treatment of chronic lymphocytic leukemia. The substances were tested for their efficacy, selectivity and bioavailability. The newly developed R26lef1 mouse model is highly adaptable, by using the Cre-loxP-system, and allows specific transgene expression in different tissues, cell types or developmental stages. The expression is stable and allows long-term experiments. The induction of expression by CD19 controlled Cre expression resulted in transgene expression in 76% of all B cells. The overexpression of LEF1 in the murine B cells leads to increased WNT signaling, which results in 3-6% less B cells in the lymphocytes of the peripheral blood, bone marrow and spleen when compared to control mice. Neither phenotypical differences of the lymphocytes nor a leukemia induction were detected in an average monitoring period of over 12 month. The overall survival was also not significantly altered, but LEF1 expressing mice developed more often cancers, which possibly reflects a reduced immune surveillance. The induction of LEF1 expression by a Cr2-cre construct revealed no significant differences to control mice. A CMV dependent Cre expression led to an abnormal skull formation resulting in a shortened snout. This phenotype is highly similar to Axin2 knock-out mice, which represent a strain with abnormally active WNT signaling. In a nutshell, the experiments show that the R26lef1 mouse model is functional and allows stable transgene expression in different tissues in long term experiments. The LEF1 overexpression in B cells seems not to hamper maturation, but rather affects proliferation. Overall LEF1 overexpression failed to induce neoplasia. In several studies, including this one, NO-ASAs, which were reported to inhibit WNT signaling, proved to be an effective and selective substances to drive chronic lymphocytic leukemia cells into apoptosis. mRNA analysis of CLL cells treated with the para isomere of NO-ASA, revealed an increased expression of heat-shock proteins and other stress related genes, which hint to an regulation by the NFκB signaling pathway. No association with WNT signaling pathway was found in this study. In order to further increase efficacy and selectivity, several derivatives of para-NO-ASA were developed. Experiments with the new NO-ASA derivatives, conducted in parallel to this study, showed an increase in selectivity and efficacy especially for two candidate substances (B9 & B12). These substances were used in in vivo experiments. B9 significantly inhibited the growth of JVM3 tumors, with a maximum inhibition ratio of 65% in a xenograft mouse model and was well tolerated (8 mg/kg, every 2nd day, intraperitoneal). B12 failed to inhibit tumor growth compared to the control group. Overall, B9 is superior to its parent compound and shows promise for a future use as a drug in the treatment of chronic lymphocytic leukemia.