Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)
Tarih
2023Yazar
Cayssials, Emilie
Turhan, Ali G.
Sorel, Nathalie
Chomel, Jean-Claude
Bennaceur-Griscelli, Annelise
Imeri, Jusuf
Desterke, Christophe
Marcoux, Paul
Telliam, Gladys
Sanekli, Safa
Barreau, Sylvain
ERBİLGİN, Yücel
Latsis, Theodoros
Hugues, Patricia
Üst veri
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Purpose: To model CML progression in vitro and generate a blast crisis (BC-CML) model in vitro in order to identify new targets. Methods: Three different CML-derived iPSC lines were mutagenized with the alkylating agent ENU on a daily basis for 60 days. Cells were analyzed at D12 of hematopoietic differentiation for their phenotype, clonogenicity, and transcriptomic profile. Single-cell RNA-Seq analysis has been performed at three different time points during hematopoietic differentiation in ENU-treated and untreated cells. Results: One of the CML-iPSCs, compared to its non-mutagenized counterpart, generated myeloid blasts after hematopoietic differentiation, exhibiting monoblastic patterns and expression of cMPO, CD45, CD34, CD33, and CD13. Single-cell transcriptomics revealed a delay of differentiation in the mutated condition as compared to the control with increased levels of MSX1 (mesodermal marker) and a decrease in CD45 and CD41. Bulk transcriptomics analyzed along with the GSE4170 GEO dataset reveal a significant overlap between ENU-treated cells and primary BC cells. Among overexpressed genes, CD25 was identified, and its relevance was confirmed in a cohort of CML patients. Conclusions: iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression.
Bağlantı
http://hdl.handle.net/20.500.12627/188581https://doi.org/10.3390/cells12040598
https://avesis.istanbul.edu.tr/api/publication/001bedcd-9599-43aa-ae83-778be134304d/file
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