In the circulating CLL pool of CD49d expressing patient subgroups, serum VCAM‐1 can bind to activated VLA‐4, triggering outside‐in signaling cascades involving ERK activation and actin polymerization, contributing to the survival of this pool during the blood journey (Fig. 3B) [129]. Here, ITGA4 is linked to B-cell chronic lymphocytic leukemia.