GATA2 Inhibition Sensitizes Acute Myeloid Leukemia Cells to Chemotherapy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Jan 24

PMID 28114350

Citations 9

Authors

Li Yang

Hanxiao Sun

Yanan Cao

Binbin Xuan

Yingchao Fan

Huiming Sheng

Wenfang Zhuang

Affiliations

Soon will be listed here.

Abstract

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.

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