| First Author | Debrincat MA | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 24 | Pages | 5850-8 |
| PubMed ID | 22374700 | Mgi Jnum | J:186573 |
| Mgi Id | MGI:5432650 | Doi | 10.1182/blood-2011-12-398834 |
| Citation | Debrincat MA, et al. (2012) Mcl-1 and Bcl-x(L) coordinately regulate megakaryocyte survival. Blood 119(24):5850-8 |
| abstractText | Mature megakaryocytes depend on the function of Bcl-x(L), a member of the Bcl-2 family of prosurvival proteins, to proceed safely through the process of platelet shedding. Despite this, loss of Bcl-x(L) does not prevent the growth and maturation of megakaryocytes, suggesting redundancy with other prosurvival proteins. We therefore generated mice with a megakaryocyte-specific deletion of Mcl-1, which is known to be expressed in megakaryocytes. Megakaryopoiesis, platelet production, and platelet lifespan were unperturbed in Mcl-1(Pf4Delta/Pf4Delta) animals. However, treatment with ABT-737, a BH3 mimetic compound that inhibits the prosurvival proteins Bcl-2, Bcl-x(L), and Bcl-w resulted in the complete ablation of megakaryocytes and platelets. Genetic deletion of both Mcl-1 and Bcl-x(L) in megakaryocytes resulted in preweaning lethality. Megakaryopoiesis in Bcl-x(Pf4Delta/Pf4Delta) Mcl-1(Pf4Delta/Pf4Delta) embryos was severely compromised, and these animals exhibited ectopic bleeding. Our studies indicate that the combination of Bcl-x(L) and Mcl-1 is essential for the viability of the megakaryocyte lineage. |
