Evaluation of Type II JAK2 Inhibitor CHZ868 resistance in B-ALL

Cytokine receptor-like factor 2 (CRLF2) is an oncoprotein whose overexpression is commonly associated with high risk B-ALL. Janus kinase (JAK) is necessary for CRLF2 signaling and JAK2 activating mutations are frequently detected in CRLF2-rearranged B-ALL. Type II JAK inhibitors, which target the inactive kinase conformation, have been shown to have enhanced efficacy compared to type I JAK inhibitors in CRLF2-rearranged human B-ALL. Acquired resistance to kinase inhibitors is a common issue and develops in many patients who are on long term kinase inhibitor therapy. Evaluation of kinase inhibitor resistance mechanisms is key due to their widespread use.