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[Gene of DNA-dependent protein kinase catalylic subunit in chronic myeloid leukemia].
- Source :
-
Zhongguo shi yan xue ye xue za zhi [Zhongguo Shi Yan Xue Ye Xue Za Zhi] 2007 Apr; Vol. 15 (2), pp. 248-52. - Publication Year :
- 2007
-
Abstract
- This study was aimed to investigate the expression and regulation mechanism of DNA-dependent protein kinase catalylic subunit (DNA-PKcs) in chronic myeloid leukemia (CML) and its role in blast crisis of CML. Expression of DNA-PKcs mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and DNA-PKcs protein by Western blot in 62 CML patients and K562, as compared to those of 23 normal individual controls. In 26 CML patients received allogeneic peripheral blood stem cell transplantation (allo-PBSCT) and 4 CML patients treated with imatinib, the expression of bcr-abl mRNA and DNA-PKcs protein was detected by RT-PCR and Western blot, respectively. After treatment with imatinib in mononuclear cell (MNC) of CML patients and K562 in vitro, expression of DNA-PKcs mRNA was detected by RT-PCR and DNA-PKcs protein level, tyrosine phosphorylation of bcr-abl fusion protein were detected by Western blot. The results showed that the expression of DNA-PKcs protein was significantly lower in CML and K562 than those in normal control (P<0.05). In 26 CML patients received allo-PBSCT and 4 CML patients treated with imatinib, the expression of DNA-PKcs protein was enhanced while the expression of bcr-abl mRNA decreased. After treatment of MNC of CML and K562 with imatinib in vitro, the expression of DNA-PKcs protein was enhanced while tyrosine phosphorylation of bcr-abl fusion protein decreased. It is concluded that the expression of DNA-PKcs protein is down-regulate by bcr-abl fusion gene, and the bcr-abl fusion gene down-regulate the expression of DNA-PKcs protein by post-transcriptional mechanism; the decrease of DNA-PKcs protein expression may be one of mechanisms underlying the acute transformation of CML.
- Subjects :
- Adult
Aged
Benzamides
Bone Marrow Cells metabolism
DNA-Activated Protein Kinase biosynthesis
Female
Fusion Proteins, bcr-abl biosynthesis
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
Male
Middle Aged
Piperazines therapeutic use
Pyrimidines therapeutic use
RNA, Messenger biosynthesis
RNA, Messenger genetics
DNA-Activated Protein Kinase genetics
Fusion Proteins, bcr-abl genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Peripheral Blood Stem Cell Transplantation
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1009-2137
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Zhongguo shi yan xue ye xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 17493325