| First Author | Menendez-Gonzalez JB | Year | 2019 |
| Journal | Stem Cell Reports | Volume | 13 |
| Issue | 2 | Pages | 291-306 |
| PubMed ID | 31378673 | Mgi Jnum | J:290781 |
| Mgi Id | MGI:6435467 | Doi | 10.1016/j.stemcr.2019.07.005 |
| Citation | Menendez-Gonzalez JB, et al. (2019) Gata2 as a Crucial Regulator of Stem Cells in Adult Hematopoiesis and Acute Myeloid Leukemia. Stem Cell Reports 13(2):291-306 |
| abstractText | Subversion of transcription factor (TF) activity in hematopoietic stem/progenitor cells (HSPCs) leads to the development of therapy-resistant leukemic stem cells (LSCs) that drive fulminant acute myeloid leukemia (AML). Using a conditional mouse model where zinc-finger TF Gata2 was deleted specifically in hematopoietic cells, we show that knockout of Gata2 leads to rapid and complete cell-autonomous loss of adult hematopoietic stem cells. By using short hairpin RNAi to target GATA2, we also identify a requirement for GATA2 in human HSPCs. In Meis1a/Hoxa9-driven AML, deletion of Gata2 impedes maintenance and self-renewal of LSCs. Ablation of Gata2 enforces an LSC-specific program of enhanced apoptosis, exemplified by attenuation of anti-apoptotic factor BCL2, and re-instigation of myeloid differentiation--which is characteristically blocked in AML. Thus, GATA2 acts as a critical regulator of normal and leukemic stem cells and mediates transcriptional networks that may be exploited therapeutically to target key facets of LSC behavior in AML. |
