Abstract
Gfi1b is a transcriptional repressor that is essential for erythroid cells and megakaryocytes, but is also expressed in hematopoietic stem cells and early myeloid progenitors. The chromosomal localization of the Gfi1b gene at 9q34 and its functional homology with the proto-oncogene Gfi1 were suggestive for a role of Gfi1b in malignant transformation and myeloid leukemia. We show here that the expression of Gfi1b is strongly elevated in CML and AML patients compared to normal healthy controls and that imatinib, a drug widely used to treat CML, further enhances Gfi1b expression in patients even after remission. Our data suggest that Gfi1b may be an important factor to establish or maintain myeloid leukemia and myeloproliferative diseases and that, high expression levels of Gfi1b might be associated with the emergence of Philadelphia chromosome negative myeloid malignancies after imatinib withdrawal or after the development of imatinib resistance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Alternative Splicing / genetics*
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Animals
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Antineoplastic Agents / therapeutic use
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Benzamides
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COS Cells
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Chlorocebus aethiops
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Chronic Disease
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Gene Expression Regulation, Neoplastic / genetics*
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Humans
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Imatinib Mesylate
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Leukemia / drug therapy
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Leukemia / genetics*
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Leukemia / metabolism*
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Piperazines / therapeutic use
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Protein Kinase Inhibitors / therapeutic use
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Mas
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Pyrimidines / therapeutic use
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RNA, Messenger / genetics
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Zinc Finger Protein GLI1
Substances
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Antineoplastic Agents
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Benzamides
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GLI1 protein, human
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MAS1 protein, human
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Piperazines
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Protein Kinase Inhibitors
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Proto-Oncogene Mas
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Pyrimidines
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RNA, Messenger
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Transcription Factors
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Zinc Finger Protein GLI1
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Imatinib Mesylate
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Protein-Tyrosine Kinases