Agglomerating Local Patterns Hierarchically with ALPHA

To increase the relevancy of local patterns discovered from noisy relations, it makes sense to formalize error-tolerance. Our starting point is to address the limitations of state-ofthe-art methods for this purpose. Some extractors perform an exhaustive search w.r.t. a declarative specification of error-tolerance. Nevertheless, their computational complexity prevents the discovery of large relevant patterns. Alpha is a 3-step method that (1) computes complete collections of closed patterns, possibly error-tolerant ones, from arbitrary n-ary relations, (2) enlarges them by hierarchical agglomeration, and (3) selects the relevant agglomerated patterns

Lymphocyte migration and retention properties affected by ibrutibnib in chronic lymphocytic leukemia

International audienceThe Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib is widely used for treatment of patients with relapsed/refractory or treatment-naïve Chronic Lymphocytic Leukemia (CLL). A prominent effect of ibrutinib is to disrupt the retention of CLL cells from supportive lymphoid tissues, by altering BTK-dependent adhesion and migration. To further explore the mechanism of action of ibrutinib and its potential impact on non-leukemic cells, we quantified multiple motility and adhesion parameters of human primary CLL cells and non-leukemic lymphoid cells. In vitro, ibrutinib affected CCL19-, CXCL12- and CXCL13-evoked migration behavior of CLL cells and non-neoplastic lymphocytes, by reducing both motility speed and directionality. Dephosphorylation of BTK induced by ibrutinib in CLL cells was associated with defective polarization over fibronectin and inability to assemble the immunological synapse upon BCR engagement. In patient samples collected during a 6-month monitoring of therapy, chemokineevoked migration was repressed in CLL cells and marginally reduced in T cells. This was accompanied by profound modulation of the expression of chemokine receptors and adhesion molecules. Remarkably, the relative expression of the receptors governing lymph node entry (CCR7) versus exit (S1PR1) stood out as a reliable predictive marker of the clinically relevant treatment-induced lymphocytosis. Together, our data reveal a multifaceted modulation of motility and adhesive properties of ibrutinib on both CLL leukemic cell and T-cell populations and point to intrinsic differences in CLL recirculation properties as underlying cause for variability in treatment response