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- Title
Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs).
- Authors
Imeri, Jusuf; Desterke, Christophe; Marcoux, Paul; Telliam, Gladys; Sanekli, Safa; Barreau, Sylvain; Erbilgin, Yucel; Latsis, Theodoros; Hugues, Patricia; Sorel, Nathalie; Cayssials, Emilie; Chomel, Jean-Claude; Bennaceur-Griscelli, Annelise; Turhan, Ali G.
- Abstract
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.
- Subjects
ALKYLATING agents; CD25 antigen; CHRONIC myeloid leukemia; CD45 antigen; PLURIPOTENT stem cells
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 4, p598
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12040598