Melatonin inhibits MLL-rearranged leukemia via RBFOX3/hTERT and NF-κB/COX-2 signaling pathways

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• MLL-rearranged leukemia is an aggressive cancer with poor prognosis and resistance to standard therapies.
• Melatonin exhibits anti-tumor properties, but its specific effects and mechanisms in MLL-rearranged leukemia are not well understood.

Purpose of the Study:

• To investigate the anti-leukemic effects of melatonin on MLL-rearranged leukemia.
• To elucidate the underlying molecular mechanisms of melatonin's action in MLL-rearranged leukemia.

Main Methods:

• In vitro studies on MLL-rearranged leukemia cell lines to assess proliferation and apoptosis.
• Mechanistic studies involving gene expression analysis (hTERT, COX-2) and protein pathway investigation (RBFOX3, NF-κB).
• Ex vivo analysis of clinical samples and in vivo xenograft mouse models to evaluate anti-leukemic activity.

Main Results:

• Melatonin inhibited MLL-rearranged leukemia cell proliferation and induced apoptosis via the caspase pathway.
• Melatonin suppressed hTERT expression by disrupting RBFOX3 binding to its promoter.
• Melatonin blocked NF-κB translocation and COX-2 expression, and demonstrated anti-leukemic effects in clinical samples and mouse models.

Conclusions:

• Melatonin exhibits significant anti-leukemic activity against MLL-rearranged leukemia.
• The anti-leukemic effects are mediated by the suppression of RBFOX3/hTERT and NF-κB/COX-2 signaling pathways.
• Melatonin represents a potential therapeutic agent for MLL-rearranged leukemia.