Abstract
The introduction of tyrosine kinase inhibitors in the treatment of BCR-ABL1-rearranged malignancies has revolutionized therapy, but the prognosis for acute leukemias remains suboptimal. In this issue of Cancer Cell, Bueno et al. (2008) add a new dimension to the regulation of ABL1 expression. The authors demonstrate that ABL1 is a direct target of miR-203, miR-203 is silenced by genetic and epigenetic mechanisms in hematopoietic malignancies expressing either ABL1 or BCR-ABL1, and restoration of miR-203 expression reduces ABL1 and BCR-ABL1 levels and inhibits cell proliferation. These findings may have broad implications for mechanisms underlying malignant transformation in hematopoietic and other malignancies.
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use
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Cell Line, Tumor
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Cell Proliferation
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DNA Methylation*
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Fusion Proteins, bcr-abl / metabolism*
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Gene Expression Regulation, Leukemic
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Gene Expression Regulation, Neoplastic*
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Gene Silencing*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Lymphoma, T-Cell / genetics
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Lymphoma, T-Cell / metabolism
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Lymphoma, T-Cell / pathology
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Lymphoproliferative Disorders / drug therapy
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Lymphoproliferative Disorders / enzymology
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / metabolism*
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Lymphoproliferative Disorders / pathology
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins c-abl / metabolism*
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Up-Regulation
Substances
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Antineoplastic Agents
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MicroRNAs
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Protein Kinase Inhibitors
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abl-bcr fusion protein, human
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Fusion Proteins, bcr-abl
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Proto-Oncogene Proteins c-abl