11 Feb Icahn Scientists Make Model of Deadly Leukemia Using CRISPR-Edited Stem Cells
MedicalResearch.com Interview with:
Eirini Papapetrou, MD, PhD
Department of Oncological Sciences
Icahn School of Medicine at Mount Sinai
New York, NY 10029
MedicalResearch.com: What is the background for this study? Would you tell us a little about acute myeloid leukemia?
Response: Acute myeloid leukemia is a form of cancer of the blood. It is typically very aggressive and lethal without treatment. The main treatment is high-dose chemotherapy and it has not changed very much in decades. Some more recent “targeted” therapies that are less toxic help somewhat but still do not result in cures. We believe a reason for this might be that both chemotherapy and newer “targeted” therapies target the cells at the later stages of the disease and spare the earlier ones, which can then give rise to disease resistance and relapse.
MedicalResearch.com: Would you describe the CRISPR gene editing tools? What is the importance of building a model of AML?Response:
Response: Most current models capture late stages of cancers, including AML. We wanted to develop a model that could capture the earlier stages and, in particular, track the progression from early stages to the fully developed AML.
To do this we used CRISPR gene editing and human induced pluripotent stem cells (iPSCs), a cell type that is particularly amenable to gene editing. CRISPR enables us to introduce specific mutations in specific genes that we know are critical to “driving” the development of AML and that we believe act at different stages (early vs late). Using CRISPR we were able to introduce these mutations with high precision in human iPSCs and, importantly, to overlay additional mutations in a sequential manner, in order to model disease progression.
MedicalResearch.com: What should readers take away from your report?
Response: Our main finding with this model so far is that, when we look at changes that drive the disease both at early and later stages, we find a lot of genes involved in inflammation and immunity. This finding and our experiments with drugs that inhibit these pathways, show that these could provide promising targets for therapies that can target the disease early.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Our study and other recent studies increasingly point to a role for inflammation in AML. We need to understand the involvement of inflammation in AML development better, especially in patients with preleukemic conditions, such as Myelodysplastic Syndrome (MDS) and Clonal Hematopoiesis (CH). A better understanding may allow us in the future to develop better treatments for AML to achieve durable responses or even cures. Also, importantly, we can perhaps use this information to develop biomarkers to identify individuals with CH and MDS who are at high risk of progression to AML and even develop ways to prevent this from happening.
Tiansu Wang, Allison R. Pine, Andriana G. Kotini, Han Yuan, Lee Zamparo, Daniel T. Starczynowski, Christina Leslie, Eirini P. Papapetrou,
Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets,
Cell Stem Cell, 2021, ISSN 1934-5909,
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Last Updated on February 11, 2021 by Marie Benz MD FAAD