Does Inhibition of Tumor Necrosis Factor Alpha Affect Tumor Growth in CML?
Posted: Tuesday, May 7, 2019
Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myeloid leukemia (CML) therapy, but they are unable to eradicate quiescent leukemia stem cells, leading to relapse in 40% to 60% of patients after treatment discontinuation. Research published in OncoTargets and Therapy found that tumor necrosis factor alpha (TNF-α) knockout impaired proliferation, colony-forming capacity, and in vivo tumorigenesis capacity of the CML K562 cell line. Additionally, apoptosis was significantly increased when TNF-α knockout cells were combined with a low concentration of imatinib.
“This study indicates that interfering TNF-α with small molecular inhibitors may be a potential approach to eliminate CML [leukemia stem cells],” stated Na Shen, PhD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues.
In the researchers’ transplantation model, TNF-α knockout delayed tumor formation—the tumor volumes and tumor weights of mice in the control group were higher than those in the TNF-α–knockout group. They also discovered that the combination of nilotinib and TNF-α inhibition reduced the colony-forming cell output of CML CD34-positive cells. TNF-α knockout inhibited the citrate cycle and promoted starch, sucrose, amino sugar, and nucleotide sugar metabolism, indicating that TNF-α is closely related to glycometabolism. Dr. Shen and colleagues noted that TNF-α may also downregulate a type of highly conserved small noncoding RNA, miR-23b-3p. This miRNA targets the cell cycle–related genes CDC6 and CDC23, resulting in cell-cycle arrest.
Disclosure: The study authors reported no conflicts of interest.