SYK has been shown to be involved in the cellular response to various microenvironmental stimuli independent of BCR engagement, including responses to CXCL12.[34] In CLL, CD38 not only marks cells with high migratory potential, it has also been identified as a modulator of CXCL12 signaling.[7,35] Our study also suggests a BCR-independent link between CD38 and SYK in their response to activation of the CXCL12-CXCR4 axis (Fig 3A). This evidence concerns the gene CXCR4 and B-cell chronic lymphocytic leukemia.