Modeling Blast Crisis Using Mutagenized Chronic Myeloid Leukemia-Derived Induced Pluripotent Stem Cells (iPSCs)

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Imeri J., Desterke C., Marcoux P., Telliam G., Sanekli S., Barreau S., ...More

Cells, vol.12, no.4, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.3390/cells12040598
  • Journal Name: Cells
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: blast crisis CML, CD25, CML modeling, iPSC, single-cell transcriptomics
  • Istanbul University Affiliated: Yes


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.