● ● ● HEMATOPOIESIS & STEM CELLS Comment on Pecquet et al, page 4625

Decreased expression of the thrombopoietin receptor (TPOR orMPL) on the cell surface of platelets andmegakaryocytes is an established feature of polycythemia vera andmyelofibrosis1,2; however, the exact mechanism responsible for this phe-nomenon has gone largely unexplained. In this issue ofBlood, Pecquet and col-leagues publish an excellent study revealing thatMPL expression is down-regulated in the context of themutant protein, JAK2V617F.3 Furthermore, JAK2V617F induces enhancedubiquination ofMPL leading to increased proteasomal degradation. The overall conse-quence of this process is reduced recycling and maturation of the receptor and lower expres-sion ofMPL on the cell surface. Notably, this finding is consistent with the previous obser-vation of defective posttranslational process-ing ofMPL and increased susceptibility to endoglycosidase H digestion inmegakaryo