The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes (original) (raw)

genes H unmutated IgV leukemia cells in vitro with preference for a subgroup of patients with The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic http://bloodjournal.hematologylibrary.org/cgi/content/full/112/4/1443 Updated information and services can be found at: (4075 articles) Neoplasia collections: Blood Articles on similar topics may be found in the following http://bloodjournal.hematologylibrary.org/misc/rights.dtl#repub\_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/misc/rights.dtl#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/subscriptions/index.dtl Information about subscriptions and ASH membership may be found online at: . Hematology; all rights reserved Src family kinases (SFKs) were described to be overexpressed in chronic lymphocytic leukemia (CLL). We wished to examine the effects of the Src and Abl kinase inhibitor dasatinib on the intracellular signaling and survival of CLL cells. Dasatinib showed a dose-and time-dependent reduction of global tyrosine phosphorylation and of activating phosphotyrosine levels of SFKs. Treatment with 100 nM dasatinib led to decreased levels of the activated, phosphorylated forms of Akt, Erk1/2, and p38, and induced PARP cleavage through caspase activity. In Mec1 and JVM-3 cell lines, dasatinib increased p53 protein levels and inhibited proliferation. In freshly isolated CLL cells, dasatinib reduced the expression of Mcl-1 and Bcl-x L . Combination of 5 M dasatinib and fludarabine increased the apoptosis induction of each by approximately 50%.

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