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Gata2Expression and Function in PML-RARA-driven Preleukemia and APL
- Source :
- Blood; November 2019, Vol. 134 Issue: 1, Number 1 Supplement 1 p534-534, 1p
- Publication Year :
- 2019
-
Abstract
- Self-renewal is a key feature of the cells that initiate acute myeloid leukemia. To identify the mechanisms involved in PML-RARA (PR)-driven self-renewal, we made use of Ctsg-PRmice, which have PRknocked into the UTR of the first exon of Ctsg. Ctsg-PRdrives the expression of PRin myeloid progenitor cells and gives these cells the ability to serially replate in methylcellulose-based colony assays. Most Ctsg-PRmice develop acute promyelocytic leukemia (APL) with an average latency of ~300 days. To identify target genes regulated by Ctsg-PR, we performed single cell RNA-seq (scRNA-seq) on whole bone marrow from young, preleukemic Ctsg-PRmice or age-matched littermates. We identified 959 differentially expressed genes (DEGs) within myeloid progenitors (546 upregulated by PR,and 413 downregulated). Gata2was identified as a DEG in this analysis, and we confirmed this phenotype with bulk RNA-seq of purified promyelocytes from young, preleukemic WT vs. Ctsg-PRmice. All APLs derived from Ctsg-PRmice also expressed high levels of Gata2.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 134
- Issue :
- 1, Number 1 Supplement 1
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs56876073
- Full Text :
- https://doi.org/10.1182/blood-2019-131883