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Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia

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Mitochondrial Shapeshifting Impacts AML Stemness and Differentiation.

Aaron D Schimmer¹

¹Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G2M9, Canada.

|July 7, 2018

Summary

Leukemic stem cells in Acute Myeloid Leukemia exhibit increased mitochondrial fission, regulated by FIS1. Targeting FIS1 and mitochondrial fission offers a new strategy to reduce cancer stemness and promote cell differentiation.

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Area of Science:

Biomedical Science
Molecular Biology
Cancer Research

Background:

Leukemic stem cells (LSCs) are crucial for Acute Myeloid Leukemia (AML) maintenance and relapse.
Understanding LSC biology is key to developing effective AML therapies.

Purpose of the Study:

To investigate the role of mitochondrial dynamics in LSC function.
To identify molecular targets for reducing LSC stemness and promoting differentiation.

Main Methods:

Analysis of mitochondrial fission in LSCs.
Investigation of the role of FIS1 in regulating mitochondrial fission.
Assessment of the impact of targeting FIS1 and mitochondrial fission on LSC properties.

Main Results:

LSCs show enhanced mitochondrial fission compared to normal hematopoietic stem cells.
FIS1 positively regulates mitochondrial fission in LSCs.
FIS1 is essential for maintaining LSC function and stemness.

Conclusions:

Targeting FIS1 expression and mitochondrial fission represents a novel therapeutic strategy for AML.
Inhibition of FIS1 and mitochondrial fission can decrease LSC stemness and enhance differentiation, potentially leading to improved treatment outcomes.