Abstract
Imatinib metylase is the first choice treatment for BCR/ABL positive chronic myelogenous leukemia (CML). However, as some CML patients develop resistance to imatinib therapy, there is a significant interest in development of alternative treatment strategies, such as identifying targets other than BCR/ABL that may participate in CML. Previously, we demonstrated strong PCNA up-regulation in CML patients. To further study its role in CML pathogenesis, we performed silencing of PCNA expression followed by array experiments. PCNA inhibition led to down-regulation of CDK1, CDK4, PLK1, ERK3, JNK1, STAT5, and several inhibitors of apoptosis (DAXX, Mdm2, survivin). The following genes were up-regulated: CDK inhibitors p21 and p19-INK4D, pro-apoptotic FAST kinase, fibronectin, etc. However, as PCNA affects cell growth in naturally proliferating cells as well as in cancerous cells, it seems to act a secondary role relating to proliferation activity of leukemic cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Benzamides
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Biomarkers, Tumor / genetics
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Cell Proliferation
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Drug Resistance, Neoplasm
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Fusion Proteins, bcr-abl / metabolism
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Gene Expression Profiling*
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Gene Expression Regulation, Leukemic*
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Gene Silencing*
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
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Oligonucleotide Array Sequence Analysis*
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Piperazines / therapeutic use
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Proliferating Cell Nuclear Antigen / genetics*
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Pyrimidines / therapeutic use
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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RNA, Small Interfering / pharmacology*
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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Benzamides
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Biomarkers, Tumor
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Piperazines
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Proliferating Cell Nuclear Antigen
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Pyrimidines
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RNA, Messenger
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RNA, Neoplasm
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RNA, Small Interfering
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Imatinib Mesylate
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Fusion Proteins, bcr-abl