Chronic myeloid leukemia stem cells: targeting therapeutic implications
Hanieh Mojtahedi1,2, Niloufar Yazdanpanah3,2,4, Nima Rezaei5,6,7
1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Stem Cell Research & Therapy
|December 19, 2021
Summary
Chronic myeloid leukemia (CML) treatment faces challenges from CML leukemic stem cells (CML LSCs) that resist therapies. Targeting CML LSCs is crucial for a functional cure beyond current tyrosine kinase inhibitor treatments.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 oncoprotein.
- Tyrosine kinase inhibitor (TKI) therapy has improved CML treatment outcomes.
- Therapy resistance and relapse are linked to CML leukemic stem cells (CML LSCs).
Purpose of the Study:
- To investigate mechanisms of TKI resistance in CML.
- To explore strategies for eradicating CML LSCs.
- To identify novel therapeutic targets for CML LSC survival.
Main Methods:
- Characterization of genetic alterations in CML LSCs.
- Analysis of molecular pathways involved in CML LSC survival.
- Investigation of the leukemic microenvironment's role in CML LSC resistance.
Main Results:
- CML LSCs possess survival mechanisms independent of BCR-ABL1 activity.
- These mechanisms contribute to intrinsic and acquired TKI resistance.
- CML LSCs exhibit resistance to apoptosis within their microenvironment.
Conclusions:
- Targeting CML LSCs is essential for achieving a functional cure for CML.
- Combination therapies involving TKIs and novel agents are promising.
- Future strategies should focus on eradicating CML LSCs while sparing normal hematopoietic stem cells.
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