Activation of Jak2 in patients with blast crisis chronic myelogenous leukemia: inhibition of Jak2 inactivates Lyn kinase

Imatinib (IM) resistance occurs in cells from chronic myelogenous leukemia (CML) patients. Resistance can be caused by mutations in the Abl kinase domain (for example, T315) 1 within Bcr-Abl or by overexpression of Bcr-Abl. Other forms of resistance to tyrosine kinase inhibitors (TKIs) exist. For example, Donato and colleagues 2 found that IM resistance can be caused by the expression of high amounts of tyrosine-phosphorylated Lyn, a member of the Src kinase family. IM resistance is attributed to the inability of IM to inhibit Lyn kinase and other Src kinase family members. The overexpression of activated Lyn kinase was also observed in the K562R cell line 2 and in cells from blast crisis (BC) CML patients. 3 Knockdown of Lyn kinase induced cell death in BC CML cells. 3 Our previous findings also showed that Jak2 kinase inhibitors induced apoptosis in BC CML cells. 4 , 5