The association of CXCR4 expression to site-specific metastasis, into BM [29, 30] of neuroblastoma-bearing patients [31], and the supportive effect of endothelial niche in Notch-dependent T-ALL cells maintenance [25, 24], favor our hypothesis that Notch3/CXCR4 crosstalk directs “pre-leukemic” DP-cells to the BM. The gene discussed is NOTCH3; the disease is acute lymphoblastic leukemia.