Tumor necrosis factor α knockout impaired tumorigenesis in chronic myeloid leukemia cells partly by metabolism modification and miRNA regulation.

ABSTRACT:

Purpose

Half of the chronic myeloid leukemia (CML) patients with sustained deep molecular response suffer from relapse after discontinuation mainly because tyrosine kinase inhibitors (TKIs) cannot eradicate leukemia stem cells (LSCs). In addition, tumor necrosis factor α (TNF-α) is highly detected in CML patients. Our aim was to explore whether TNF-α is a potential target for LSC elimination.

Materials and methods

We applied a CRISPR/Cas9 gene editing technique, colony-forming cell assay, subcutaneous tumor models, miRNA-seq and liquid chromatography-mass spectroscopy (LC-MS) on metabonomics to explore the feasibility and mechanism of TNF-α as a new therapeutic target for CML.

Results

We demonstrated that TNF-α knockout remarkably decreased the proliferative, colony-f

SUBMITTER: Shen N 

PROVIDER: S-EPMC6446984 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature