Modeling Transient Abnormal Myelopoiesis Using Induced Pluripotent Stem Cells and CRISPR/Cas9 Technology.

ABSTRACT: Approximately 1%-2% of children with Down syndrome (DS) develop acute myeloid leukemia (AML) prior to age 5 years. AML in DS children (ML-DS) is characterized by the pathognomonic mutation in the gene encoding the essential hematopoietic transcription factor GATA1, resulting in N-terminally truncated short form of GATA1 (GATA1s). Trisomy 21 and GATA1s together are sufficient to induce transient abnormal myelopoiesis (TAM) exhibiting pre-leukemic characteristics. Approximately 30% of these cases progress into ML-DS by acquisition of additional somatic mutations. We employed disease modeling in vitro by the use of customizable induced pluripotent stem cells (iPSCs) to generate a TAM model. Isogenic iPSC lines derived from the fibroblasts of DS individuals with trisomy 21 and wi

SUBMITTER: Barwe SP 

PROVIDER: S-EPMC7558799 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature