Mitochondrial Dysfunction in Apoptosis-Resistant Acute Myeloid Leukemia Cells During a Sterile Inflammatory Response

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Mitochondria play vital roles in energy metabolism, apoptosis, and inflammation in acute myeloid leukemia (AML).
• Apoptosis resistance is a hallmark of AML, contributing to treatment failure.

Purpose of the Study:

• To investigate mitochondrial alterations in apoptosis-resistant AML cells under aseptic pro-inflammatory activation.
• To understand the metabolic reprogramming of AML cells during inflammatory stress.

Main Methods:

• Spectrofluorimetry, qPCR, Western blotting, gene expression analysis, flow cytometry, transmission electron microscopy, and cellular respiration analysis.
• In vitro aseptic pro-inflammatory activation of AML cells in 3D high-density cultures.

Main Results:

• Apoptosis-resistant AML cells showed reduced oxidative phosphorylation and tricarboxylic acid cycle gene activity.
• Diminished mitochondrial respiration, decreased PINK1/Parkin levels, and increased reactive oxygen species were observed.
• Pathogenic mitochondrial morphology changes, including elevated DRP1 and increased small/medium mitochondria, were noted, alongside lactate accumulation.

Conclusions:

• Aseptic pro-inflammatory activation induces metabolic remodeling and mitochondrial dysfunction in AML cells.
• This reprogramming may enhance leukemic cell persistence and contribute to apoptosis resistance.
• The study establishes a model for investigating AML cell metabolism and anti-apoptotic mechanisms.