Modeling Global Genomic Instability in Chronic Myeloid Leukemia (CML) Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs).

ABSTRACT:

Methods

We used a patient-specific induced pluripotent stem cell (iPSC) line treated with the mutagenic agent N-ethyl-N-nitrosourea (ENU). Genomic instability was validated using γ-H2AX and micronuclei assays and CGH array for genomic events.

Results

An increased number of progenitors (x5-Fold), which proliferated in liquid cultures with a blast cell morphology, was observed in the mutagenized condition as compared to the unmutagenized one. CGH array performed for both conditions in two different time points reveals several cancer genes in the ENU-treated condition, some known to be altered in leukemia (BLM, IKZF1, NCOA2, ALK, EP300, ERG, MKL1, PHF6 and TET1). Transcriptome GEO-dataset GSE4170 allowed us to associate 125 of 249 of the aberrations that we detected in CML-iPSC

SUBMITTER: Telliam G 

PROVIDER: S-EPMC10177163 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature