CD126 and targeted therapy with Tocilizumab in Chronic Lymphocytic Leukemia

Purpose: Experimental Design:The levels of membrane-bound CD126 expression were determined on freshly isolated CLL B-cells (n=58) using flow cytometry. These CLL cells were treated with Chlorambucil (CBL) or Fludarabine with or without anti-CD126 antibody Tocilizumab for 24 hours and IL-6-mediated STAT3 transcriptional activity and cell cycle alteration were evaluated. Results: CD126 surface expression was found in all cases and positively correlated with the levels of in vivo constitutive STAT3 activity. The levels of CD126 expression were significantly and positively correlated with the resistance of CLL cells to in vitro treatment with CBL or Fludarabine and poor in vivo treatment response of CLL patients. Blocking IL-6 signaling with the anti-CD126 antibody, Tocilizumab, had profound effects on STAT3-mediated survival and growth signals: decreased Mcl-1 and Bcl-xL, favoring an apoptotic profile; and decreased p27 with increased cyclin E and CDK2 expression, leading to cell cycle shift from G0 to G1. These Tocilizumab-mediated changes induced chemo-sensitization in resistant CLL cells, with the greatest effect seen in cells with higher CD126 expression (P<0.001). Conclusions: CLL cells with higher CD126 expression are more resistant to treatment in vivo and in vitro via IL-6-CD126-STAT3 axis. Blockade CD126 using Tocilizumab sensitizes CLL cells to chemotherapy.

from Cancer via ola Kala on Inoreader http://ift.tt/1QTn3ZT
via IFTTT