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Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia
Mark D McKenzie1, Margherita Ghisi2, Ethan P Oxley2
1Molecular Medicine Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.
Cell Stem Cell
|August 3, 2019
Summary
Mature leukemia cells can revert to a cancer stem cell state in acute myeloid leukemia (AML). This plasticity challenges therapies targeting only immature cancer stem cells (CSCs), necessitating broader treatment strategies.
Area of Science:
- Oncology
- Hematology
- Cell Biology
Background:
- Tumors exhibit cellular heterogeneity, with cancer stem cells (CSCs) thought to drive tumor propagation through differentiation.
- Therapeutic strategies often target CSCs or aim to induce their differentiation, assuming a unidirectional maturation process.
Purpose of the Study:
- To investigate the plasticity of cancer stem cell maturation in acute myeloid leukemia (AML).
- To determine if mature leukemia cells can revert to a more primitive, cancer-propagating state.
Main Methods:
- Utilized murine and human models of AML.
- Manipulated the expression of the transcription factor PU.1.
- Withdrew established differentiation therapies.
Main Results:
- Demonstrated that mature AML cells can de-differentiate.
- Showed that these de-differentiated cells reacquire clonogenic and leukemogenic properties.
- Identified plasticity in CSC maturation within AML models.
Conclusions:
- Cancer stem cell maturation in AML is not a unidirectional process.
- Therapeutic strategies must consider the potential for mature leukemia cells to regain stem-like properties.
- Eradicating cancer cells across diverse differentiation states is crucial for effective AML treatment.
Keywords:
PU.1acute myeloid leukemiaacute promyelocytic leukemiacancer stem celldifferentiation therapyleukemia stem cellmyelopoiesispioneer factorretinoic acidtranscription factorMore Related Videos
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