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System and method for killing chronic myelogenous leukemia drug-resistant cells

A technology of chronic granulocytes and drug-resistant cells, applied in the field of medical basic research, can solve problems such as large toxic side effects and limitations

Inactive Publication Date: 2015-12-23
CHONGQING MEDICAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the third-generation TKI specifically targeting BCR-ABLT315I has been released, its clinical use is limited by the problem of too many toxic and side effects. Therefore, it is still necessary to find new therapeutic strategies to overcome the problem of clinical drug resistance

Method used

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  • System and method for killing chronic myelogenous leukemia drug-resistant cells
  • System and method for killing chronic myelogenous leukemia drug-resistant cells
  • System and method for killing chronic myelogenous leukemia drug-resistant cells

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Embodiment Construction

[0041] Such as figure 1 As shown, a system for killing chronic myelogenous leukemia drug-resistant cells consists of SH2-PTP1B / C-ODC fusion gene and AZ1 gene loaded into adenovirus; the SH2-PTP1B / C-ODC fusion gene and AZ1 The gene loaded adenovirus is Ad5 adenovirus.

[0042] The nucleotide sequence of the SH2-PTP1B / C-ODC fusion gene is shown in SEQ ID No.1;

[0043] The nucleotide sequence of the AZ1 gene is shown in SEQ ID No.2.

[0044] A method for killing chronic myelogenous leukemia drug-resistant cells, respectively preparing Ad5 recombinant adenoviruses loaded with SH2-PTP1B / C-ODC fusion gene and AZ1 gene; infecting CML cells, expressing SH2-PTP1B / C-ODC in CML cells ODC fusion protein and AZ1 protein; PTP1B / C dephosphorylates Y177 and inhibits BCR-ABL activity through the combination of SH2 and BCR-ABLY177; at the same time, BCR-ABL is labeled with ODC by SH2 signal, in the case of co-expression of AZ1 In this way, BCR-ABL was introduced into the ODC-AZ1 non-ubiquit...

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Abstract

The invention provides a system for killing chronic myelogenous leukemia drug-resistant cells. The system is composed of SH2-PTP1B / C-ODC fused genes in which adenovirus is loaded and AZ1 genes. It is proved by experiments that by means of the system and method, the leukemia drug-resistant cells can be killed, the effect is quite good, and the system and method have quite high research value on leukemia treatment research and drug development.

Description

technical field [0001] The invention relates to the field of basic medical research, in particular to a system and method for killing leukemia drug-resistant cells. Background technique [0002] Chronic myeloid leukemia (CML) is a common malignant tumor of the blood system. If not treated properly, patients will progress from chronic phase to irreversible blast phase within 5 years and lose their lives. The main pathogenesis of CML is due to the t(9,22)(q34,q11) balanced translocation of the c-abl gene on chromosome 9 and the bcr gene on chromosome 22, forming a bcr-abl fusion gene, which encodes a gene with high tyrosine Kinase-active BCR-ABL fusion protein, which activates downstream RAS-MAPK, PI3K-AKT, STAT5, CRKL and other signaling pathways, leading to uncontrolled cell proliferation and blocked apoptosis. The clinical first-line treatment drug imatinib is a tyrosine kinase inhibitor (tyrosine kinase inhibitor, TKI), which competitively inhibits the combination of ATP ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/861C12N5/10
Inventor 冯文莉高淼黄峥兰徐敏
Owner CHONGQING MEDICAL UNIVERSITY
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