Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Inhibition of GATA2 restrains cell proliferation and enhances apoptosis and chemotherapy mediated apoptosis in human GATA2 overexpressing AML cells

Menendez Gonzalez, Juan Bautista, Sinnadurai, Samantha, Gibbs, Alex, Thomas, Leigh-Anne, Konstantinou, Maria, Garcia Valverde, Alfonso, Boyer, Magali, Wang, Zhengke, Boyd, Ashleigh S., Blair, Allison, Morgan, Rhys G. and Rodrigues, Neil P. 2019. Inhibition of GATA2 restrains cell proliferation and enhances apoptosis and chemotherapy mediated apoptosis in human GATA2 overexpressing AML cells. Scientific Reports 9 , 12212. 10.1038/s41598-019-48589-0

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
[img]
Preview
Image (TIFF) (Fig1) - Supplemental Material
Download (2MB) | Preview
[img]
Preview
Image (TIFF) (Fig2) - Supplemental Material
Download (2MB) | Preview
[img]
Preview
Image (TIFF) (Fig3) - Supplemental Material
Download (2MB) | Preview
[img]
Preview
Image (TIFF) (Fig4) - Supplemental Material
Download (2MB) | Preview

Abstract

GATA2, a zinc finger transcription factor predominantly expressed in hematopoietic cells, acts as an essential regulator of hematopoietic stem cell generation, survival and functionality. Loss and gain of GATA2 expression has been implicated in myelodysplastic syndrome and acute myeloid leukemia (AML) yet the precise biological impact of GATA2 expression on human AML cell fate decisions remains ambiguous. Herein, we performed large-scale bioinformatics that demonstrated relatively frequent GATA2 overexpression in AML patients as well as select human AML (or AML-like) cell lines. By using shRNAi to target GATA2 in these AML cell lines, and an AML cell line expressing normal levels of GATA2, we found that inhibition of GATA2 caused attenuated cell proliferation and enhanced apoptosis exclusively in AML cell lines that overexpress GATA2. We proceeded to pharmacologically inhibit GATA2 in concert with AML chemotherapeutics and found this augmented cell killing in AML cell lines that overexpress GATA2, but not in an AML cell line expressing normal levels of GATA2. These data indicate that inhibition of GATA2 enhances chemotherapy-mediated apoptosis in human AML cells overexpressing GATA2. Thus, we define novel insights into the oncogenic role of GATA2 in human AML cells and suggest the potential utilization of transient GATA2 therapeutic targeting in AML.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Publisher: Nature Research
ISSN: 2045-232
Date of First Compliant Deposit: 8 August 2019
Date of Acceptance: 7 August 2019
Last Modified: 17 Oct 2019 02:40
URI: http://orca-mwe.cf.ac.uk/id/eprint/124814

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics