Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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B-Lymphocytes / drug effects*
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B-Lymphocytes / metabolism
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B-Lymphocytes / pathology
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Cell Line, Tumor
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Cell Survival / drug effects
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Dasatinib
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G1 Phase Cell Cycle Checkpoints / drug effects
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Granulocyte Precursor Cells / drug effects*
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Granulocyte Precursor Cells / metabolism
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Granulocyte Precursor Cells / pathology
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Humans
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Leukemia, Prolymphocytic, B-Cell / genetics
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Leukemia, Prolymphocytic, B-Cell / metabolism*
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Leukemia, Prolymphocytic, B-Cell / pathology
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Mutation*
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology*
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Pyrimidines / pharmacology*
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / metabolism
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Thiazoles / pharmacology*
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Time Factors
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Tumor Suppressor Protein p53 / genetics*
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrimidines
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STAT3 Transcription Factor
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STAT3 protein, human
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TP53 protein, human
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Thiazoles
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Tumor Suppressor Protein p53
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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Dasatinib