The mutual activation of stromal cells and tumor cells also depends on the CLL-mediated activation of Notch2 in BM stromal cells, leading to C1q overexpression the reciprocal activation of the canonical Wnt pathway in CLL cells (84) Moreover, BM stromal cell derived CXCL12 exhibits a pro-survival effect on CLL tumor cells (44, 85, 86). This evidence concerns the gene NOTCH2 and B-cell chronic lymphocytic leukemia.