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Ibrutinib Inhibits B-cell Adhesion in Chronic Lymphocytic Leukemia Patients Leading to a Transient Treatment Induced Lymphocytosis.

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • R.Z. Mustafa
  • S.E Herman
  • M. Farooqui
  • N. Saba
  • J.E. Jones
  • A. Wiestner


Chronic lymphocytic leukemia (CLL) is characterized by the expansion of monoclonal, mature CD5+/CD23+ B-cells. Currently, no chemotherapeutic strategies are considered curative and many patients cannot tolerate intensive chemotherapy. This provides rationale for development of novel agents that target signaling pathways related to the pathogenesis of CLL. The B-cell receptor (BCR) regulates the survival, proliferation, and migration of B-cells. Bruton’s tyrosine kinase (BTK) is activated downstream of the BCR and is essential for signal transduction by the BCR. Ibrutinib, which irreversibly binds BTK and inhibits its enzymatic activity, has shown to be well tolerated and induce objective clinical responses. Surprisingly, in the first week on ibrutinib a transient increase of tumor cells in the blood is seen in most patients. In order to investigate the mechanism of this lymphocytosis, we evaluated the in vivo effect of ibrutinib on CLL cell adhesion. After one day on ibrutinib we observed a significant increase in CD38 and Ki67. Consistently, we found that ibrutinib directly inhibits adhesion of CLL cells to fibronectin (median reduction of 95%; P <0.05). Our findings suggest that ibrutinib leads to a release of cells from the tissue compartment into the blood, due in part to a disruption of B-cell adhesion.

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