CD49d, the alpha chain of the very late antigen-4 (VLA-4) integrin, has a negative prognostic impact in chronic lymphocytic leukemia treated with the Bruton's tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib. Despite BTK inhibition, VLA-4 remains inside-out activated via B-cell receptor, an activation dampened by phosphoinositide 3-kinase inhibitors. Evaluation of CD49d expression in patients starting BTK inhibitor therapy may improve their prognostic stratification. See related article by Alsadhan et al., p. 3612.
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