{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:07:39Z","timestamp":1792019259672,"version":"4.4.0"},"reference-count":46,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,25]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>B-cell receptor (BCR) signaling is a key determinant of chronic lymphocytic leukemia (CLL) pathophysiology. CD49d, the \u03b14 subunit of the very late antigen 4 integrin, can be activated by BCR signals; however, its role in modulating BCR functionality remains unknown. We used knockout mouse models and primary human CLL stratified by CD49d expression to address this aspect. CD49d was required for bone marrow (BM) infiltration and shaped BM infiltration patterns and patient outcomes in human CLL. In TCL1 transplantation models, the loss of CD49d abrogated BM homing and leukemic cell positioning within splenic niches. At the cellular level, CD49d-deficient murine TCL1 transgenic cells and human CD49d-low CLL cells failed to form efficient immune synapses with antigen-presenting membranes. Transcriptome analyses identified CD49d-dependent regulation of actin-associated pathways and distinct signatures of BCR responsiveness in both human and mouse cells. Consistently, CD49d-low human CLL cells displayed aberrant actin remodeling following BCR stimulation, and a second aggressive murine CLL model reproduced the actin and engraftment defects. Kinome profiling linked impaired antigen-induced BCR responses in CD49d-deficient murine cells to altered kinase activity, and pharmacologic actin perturbation phenocopied CD49d loss. In human CD49d-low CLL cells, a desynchronization of BCR-related downstream Syk and PLC\u02632 activation was found. Mechanistically, the CD49d-BCR interplay involved their colocalization, and CD49d converged with BCR signaling on a focal adhesion kinase\u2013actin axis. In summary, our findings establish CD49d as a key regulator of BCR functionality in CLL, linking integrins to cytoskeletal dynamics and antigen responsiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024027753","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:56:11Z","timestamp":1772819771000},"page":"3179-3194","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":2,"title":["CD49d governs immune synapse formation through actin rearrangements and synchronizes BCR signaling in CLL"],"prefix":"10.1182","volume":"147","author":[{"given":"Laura","family":"Polcik","sequence":"first","affiliation":[{"name":"1Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany"},{"name":"2University of Freiburg, Faculty of Biology, Freiburg, 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