Hypoxia attenuates growth of MPN cells through suppression of SHP-2 expression and subsequent inhibition of JAK2V617F activity

我们发现，低氧抑制JAK2V617F的活性，并诱导JAK2V617F阳性的MPN细胞生长停滞。SHP-2在这些过程中起着重要的作用。有趣的是，一些研究已经报道了SHP-2是细胞因子激活JAK2所必需的。此外，最近的研究表明，MPN患者的血小板中SHP-2的活性增加。综上所述，低氧环境可能通过抑制SHP-2水平进而抑制JAK2V617F活性来调控JAK2阳性MPN细胞的命运。

We found that hypoxia suppressed activity of JAK2V617F and induced growth arrest in JAK2V617F-positive MPN cells. SHP-2 plays important roles in these process. Interestingly, several studies have reported that SHP-2 is required for the activation of JAK2 by cytokines. In addition, recent studies have revealed that the activity of SHP-2 is increased in platelets from MPN patients. In conclusion, hypoxic environment may modulate fate of JAK2-positive MPN cells through suppression of SHP-2 levels and subsequent suppression of JAK2V617F activity.