TY - JOUR T1 - Anti-leukemic activity of dasatinib in both p53(wild-type) and p53(mutated) B malignant cells. JF - Invest New Drugs Y1 - 2012 A1 - Bosco, Raffaella A1 - Rabusin, Marco A1 - Voltan, Rebecca A1 - Celeghini, Claudio A1 - Corallini, Federica A1 - Capitani, Silvano A1 - Secchiero, Paola KW - Antineoplastic Agents KW - Apoptosis KW - B-Lymphocytes KW - Cell Line, Tumor KW - Cell Survival KW - G1 Phase Cell Cycle Checkpoints KW - Granulocyte Precursor Cells KW - Humans KW - Leukemia, Prolymphocytic, B-Cell KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinase 3 KW - Mutation KW - p38 Mitogen-Activated Protein Kinases KW - Phosphorylation KW - Protein Kinase Inhibitors KW - Pyrimidines KW - STAT3 Transcription Factor KW - Thiazoles KW - Time Factors KW - Tumor Suppressor Protein p53 AB -

The multi-kinase inhibitor dasatinib induced a variable but significant decrease of viability in both p53(wild-type) (EHEB, JVM-2, JVM-3) and p53(mutated) (MEC-1, MEC-2, BJAB) prolymphocytic B leukemic cells, due to a combination of cell cycle block in G1 and apoptosis. Antibody phospho-kinase array analysis revealed that dasatinib inhibited the phosphorylation of various kinases, including ERK1/2 and p38/MAPK as well as of STAT3 transcription factors, in both p53(wild-type) and p53(mutated) cells. Therefore, dasatinib might offer a novel therapeutic strategy not only for p53(wild-type), but also for p53(mutated) B malignancies that have the worst prognosis and urgently need innovative therapeutic approaches.

VL - 30 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20953816?dopt=Abstract ER -