| First Author | Guezguez B | Year | 2016 |
| Journal | Cancer Cell | Volume | 29 |
| Issue | 1 | Pages | 61-74 |
| PubMed ID | 26766591 | Mgi Jnum | J:231320 |
| Mgi Id | MGI:5770188 | Doi | 10.1016/j.ccell.2015.11.012 |
| Citation | Guezguez B, et al. (2016) GSK3 Deficiencies in Hematopoietic Stem Cells Initiate Pre-neoplastic State that Is Predictive of Clinical Outcomes of Human Acute Leukemia. Cancer Cell 29(1):61-74 |
| abstractText | Initial pathway alternations required for pathogenesis of human acute myeloid leukemia (AML) are poorly understood. Here we reveal that removal of glycogen synthase kinase-3alpha (GSK-3alpha) and GSK-3beta dependency leads to aggressive AML. Although GSK-3alpha deletion alone has no effect, GSK-3beta deletion in hematopoietic stem cells (HSCs) resulted in a pre-neoplastic state consistent with human myelodysplastic syndromes (MDSs). Transcriptome and functional studies reveal that each GSK-3beta and GSK-3alpha uniquely contributes to AML by affecting Wnt/Akt/mTOR signaling and metabolism, respectively. The molecular signature of HSCs deleted for GSK-3beta provided a prognostic tool for disease progression and survival of MDS patients. Our study reveals that GSK-3alpha- and GSK-3beta-regulated pathways can be responsible for stepwise transition to MDS and subsequent AML, thereby providing potential therapeutic targets of disease evolution. |
