Leukemia Cells Resistant to Glutamine Deprivation Express Glutamine Synthetase Protein

Overview

Journal Turk J Haematol

Specialty Hematology

Date 2021 Apr 22

PMID 33882633

Citations 1

Authors

Burcu Yucel

Saniye Ada

Affiliations

Soon will be listed here.

Abstract

Objective: Low glutamine levels have been shown in tumor environments for several cancer subtypes. Therefore, it has been suggested that cancer cells rewire their metabolism to adopt low nutrient levels for survival and proliferation. Although glutamine is a non-essential amino acid and can be synthesized de novo, many cancer cells including malignant hematopoietic cells have been indicated to be addicted to glutamine. This study aimed to investigate the proliferation of leukemia cell lines in glutamine-deprived conditions.

Materials And Methods: Cell proliferation of K562, NB-4, and HL-60 cells was determined by calculating cell numbers in normal vs. low glutamine media. Changes in mRNA expressions were investigated using qRT-PCR. The glutamine synthetase (GS)-encoding gene was knocked out (KO) in HL-60 cells using the CRISPR/Cas9 method and protein expression was evaluated with immunoblotting.

Results: The proliferation of all cell lines was decreased in glutamine-deprived medium. GS protein expression was increased in glutamine-limited medium although the mRNA level did not change. Increased protein expression was confirmed with inhibition of new protein synthesis by treating cells with cycloheximide. To further investigate the role of GS protein, the GS-encoding gene was KO in HL-60 cells using the CRISPR/Cas9 method. GS KO cells proliferated less compared to control cells in glutamine-limited medium.

Conclusion: Our results indicate that upregulated GS protein expression is responsible for glutamine addiction of leukemia cell lines. Exploiting the genetic and metabolic mechanisms responsible for GS protein expression could lead to the identification of new anti-cancer drug targets.

Citing Articles

AMPK Activation in TET2 Downregulated Leukemia Cells Upon Glutamine Limitation.

Bayrak A, Yucel B Medeni Med J. 2024; 39(3):161-168.

PMID: 39350522 PMC: 11572213. DOI: 10.4274/MMJ.galenos.2024.59683.

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