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

我们发现缺氧抑制JAK 2 V617 F的活性，并诱导JAK 2 V617 F阳性MPN细胞的生长停滞。SHP-2在这些过程中起着重要作用。有趣的是，一些研究报道了SHP-2是细胞因子激活JAK 2所必需的。此外，最近的研究表明，在来自MPN患者的血小板中，SHP-2的活性增加。总之，低氧环境可能通过抑制SHP-2水平和随后抑制JAK 2 V617 F活性来调节JAK 2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.