GATA2 Inhibition Sensitizes Acute Myeloid Leukemia Cells to Chemotherapy

Autor: Huiming Sheng, Yingchao Fan, Li Yang, Binbin Xuan, Wenfang Zhuang, Hanxiao Sun, Yanan Cao
Rok vydání: 2017
Předmět:
0301 basic medicine
Myeloid
medicine.medical_treatment
Cancer Treatment
lcsh:Medicine
Apoptosis
Artificial Gene Amplification and Extension
Drug resistance
Polymerase Chain Reaction
Hematologic Cancers and Related Disorders
hemic and lymphatic diseases
Medicine and Health Sciences
lcsh:Science
Cultured Tumor Cells
education.field_of_study
Multidisciplinary
Cell Death
Pharmaceutics
GATA2
Myeloid leukemia
Hematology
Myeloid Leukemia
Leukemia
medicine.anatomical_structure
Oncology
Cell Processes
Biological Cultures
Research Article
medicine.drug
Acute Myeloid Leukemia
Clinical Oncology
Population
Research and Analysis Methods
Cancer Chemotherapy
03 medical and health sciences
Gefitinib
Drug Therapy
Leukemias
medicine
Chemotherapy
Leukemia Cells
Molecular Biology Techniques
education
Molecular Biology
business.industry
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
Cell Cultures
medicine.disease
030104 developmental biology
Cancer research
lcsh:Q
Clinical Medicine
business
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 1, p e0170630 (2017)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0170630
Popis: Drug resistance constitutes one of the main obstacles for clinical recovery of acute myeloid leukemia (AML) patients. Therefore, the treatment of AML requires new strategies, such as adding a third drug. To address whether GATA2 could act as a regulator of chemotherapy resistance in human leukemia cells, we observed KG1a cells and clinical patients' AML cells with a classic drug (Cerubidine) and Gefitinib. After utilizing chemotherapy, the expression of GATA2 and its target genes (EVI, SCL and WT1) in surviving AML cells and KG1a cells were significantly enhanced to double and quadrupled compared to its original level respectively. Furthermore, with continuous chemotherapeutics, AML cells with GATA2 knockdown or treated with GATA2 inhibitor (K1747) almost eliminated with dramatically reduced expression of WT1, SCL, EVI, and significantly increased apoptotic population. Therefore, we propose that reducing GATA2 expression or inhibition of its transcription activity can relieve the drug resistance of acute myeloid leukemia cells and it would be helpful for eliminating the leukemia cells in patients.
Databáze: OpenAIRE
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