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Published on: January 7, 2019
Programmed cell death 4 and BCR-ABL fusion gene expression are negatively correlated in chronic myeloid leukemia
Xia Zhang1, Riming Liu1, Baohua Huang1
1Department of Laboratory Medicine, Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
Abstract:
Programmed cell death 4 (PDCD4) is a tumor suppressor that inhibits carcinogenesis, tumor progression and invasion by preventing gene transcription and translation. Downregulation of PDCD4 expression has been identified in multiple types of human cancer, however, to date, the function of PDCD4 in leukemia has not been investigated. In the present study, PDCD4 mRNA and protein expression was investigated in 50 patients exhibiting various phases of chronic myeloid leukemia (CML) and 20 healthy individuals by reverse transcription-quantitative polymerase chain reaction and western blot analysis. PDCD4 expression and cell proliferation was also investigated following treatment with the tyrosine kinase inhibitor, imatinib, in K562 cells. The results demonstrated that PDCD4 mRNA and protein expression was decreased in all CML samples when compared with healthy controls, who expressed high levels of PDCD4 mRNA and protein. No significant differences in PDCD4 expression were identified between chronic phase, accelerated phase and blast phase CML patients. In addition, PDCD4 expression was negatively correlated with BCR-ABL gene expression (r=-0.6716; P<0.001). Furthermore, K562 cells treated with imatinib exhibited significantly enhanced PDCD4 expression. These results indicate that downregulation of PDCD4 expression may exhibit a critical function in the progression and malignant proliferation of human CML.
Insights
Programmed cell death 4 (PDCD4) is a tumor suppressor. Its expression is decreased in chronic myeloid leukemia (CML), suggesting PDCD4 plays a role in CML progression and proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Programmed cell death 4 (PDCD4) acts as a tumor suppressor by inhibiting gene transcription and translation.
- PDCD4 downregulation is observed in various human cancers, but its role in leukemia remains unclear.
Purpose of the Study:
- To investigate PDCD4 expression in chronic myeloid leukemia (CML).
- To explore the correlation between PDCD4 expression and CML progression.
- To examine PDCD4 modulation by imatinib in CML cells.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used.
- PDCD4 and BCR-ABL gene expression were quantified in CML patients and healthy controls.
- K562 cells were treated with imatinib to assess PDCD4 expression and proliferation.
Main Results:
- PDCD4 mRNA and protein levels were significantly decreased in all CML patients compared to healthy controls.
- No significant differences in PDCD4 expression were found across different CML phases.
- PDCD4 expression showed a negative correlation with BCR-ABL gene expression (r=-0.6716; P<0.001).
- Imatinib treatment led to significantly enhanced PDCD4 expression in K562 cells.
Conclusions:
- Downregulation of PDCD4 may be critical in the malignant proliferation and progression of CML.
- PDCD4's tumor-suppressive function warrants further investigation in the context of leukemia.
- Targeting PDCD4 could be a potential therapeutic strategy for CML.
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