| First Author | Spivak JL, Williams DM, Zhao ZJ, Rogers O, Duffield AS, Hankins WD, Moliterno AR | Year | 2015 |
| Journal | Blood | Volume | 126 |
| Issue | 23 | Pages | 484 |
| Mgi Jnum | J:331302 | Mgi Id | MGI:7387055 |
| Doi | 10.1182/blood.V126.23.484.484 | Citation | Spivak JL, Williams DM, Zhao ZJ, Rogers O, Duffield AS, Hankins WD, Moliterno AR (2015) MPL SV, a Unique MPN MPL Splice Variant, Provokes a Fulminant Myeloid Leukemia in a JAK2 V617F Transgenic Mouse Model of Polycythemia Vera. Blood 126(23):484 |
| abstractText | The MPN, polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) are clonal stem cell disorders, which share mutations constitutively activating the physiologic signal transduction pathways for hematopoiesis. Although the MPN have different natural histories, they share in common transformation to myelofibrosis and acute leukemia at differing frequencies and not explainable by a specific mutation. Impaired MPL expression, due to incomplete glycosylation is another common denominator amongst the MPN. Significantly, MPL is the only hematopoietic growth factor receptor expressed in MPN HSC, and we have demonstrated that the PV phenotype in a JAK2 V617F transgenic (V617tg) mouse could be abrogated by elimination of MPL or its ligand, TPO. Impaired MPL expression in the MPN cannot be completely explained by receptoractivated down regulation because not all MPN driver mutations directly activate MPL. However, we have discovered another common denominator in the MPN, variant MPL splicing, eliminating 7 amino acids in the MPL N-terminal domain, a common hotspot for both MPL driver and inactivating mutations, which impairs MPL glycosylation and expression. |
