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Most of these proteins behave as receptors to link adhesion to the control of cell survival and their expression or regulation are often altered in cancers. B\u2010cell malignancies do not evade this principle as they are sustained in relapsed niches by interacting with the microenvironment that includes cells and their secreted factors. Focusing on chronic lymphocytic leukemia and mantle cell lymphoma, this Review delves with the molecules involved in the dialog between the adhesion platforms and signaling pathways known to regulate both cell adhesion and survival. Current therapeutic strategies disrupt adhesive structures and compromise the microenvironment support to tumor cells, rendering them sensitive to immune recognition. The development of organ\u2010on\u2010chip and 3D culture systems, such as spheroids, have revealed the importance of mechanical cues in regulating signaling pathways to organize cell adhesion and survival. 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