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Using Human Induced Pluripotent Stem Cells for the Generation of Tumor Antigen-specific T Cells
Published on: October 24, 2019
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Studying clonal evolution of myeloid malignancies using induced pluripotent stem cells
Sergei Doulatov1,2,3, Eirini P Papapetrou4,5,6,7
1Division of Hematology, Department of Medicine.
Current Opinion in Hematology
|December 2, 2020
Summary
Induced pluripotent stem cells (iPSCs) help untangle complex myeloid malignancies by capturing patient cell genomes and enabling precise genetic editing. This technology illuminates clonal evolution and aids in drug discovery for myelodysplastic syndromes and acute myeloid leukemia.
Area of Science:
- Hematology
- Cancer Genomics
- Stem Cell Biology
Background:
- Myeloid malignancies are genetically diverse, characterized by stepwise mutations and clonal evolution.
- Patient blood and bone marrow contain complex mixtures of clones and subclones, difficult to analyze with current methods.
Purpose of the Study:
- To review the application of induced pluripotent stem cell (iPSC) technology in studying clonal architecture and evolution in myeloid malignancies.
- Focus on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
Main Methods:
- Reprogramming somatic cells to iPSCs to capture their genomes.
- Utilizing precise genome editing to introduce specific driver mutations into normal iPSCs.
- Analyzing clonal composition, mutational order, and functional consequences of mutations.
Main Results:
- iPSC technology enables elucidation of clonal composition and mutational order in myeloid neoplasms.
- Allows functional interrogation of individual and combined mutations' cellular and molecular consequences.
- Facilitates drug testing against distinct disease clones.
Conclusions:
- Human iPSCs are crucial tools for understanding the progression from normal to malignant hematopoiesis.
- iPSC technology empowers drug testing and discovery for myeloid malignancies like MDS and AML.
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