Type II JAK2 Inhibitor NVP-CHZ868 is Active in Vitro and in Vivo Against JAK2-Dependent B-cell Acute Lymphoblastic Leukemias. Homo sapiens

Gene expression profiling was performed to define transcriptional programs associated with response to type II JAK2 inhibitor NVP-CHZ868 alone or in combination with dexamethasone in vitro and in vivo. Overall design: MHH-CALL4 cells harboring a CRLF2 rearrangement and JAK2 I682F mutation were treated with vehicle, CHZ868, dexamethasone, or CHZ868 + dexamethasone combination for 12 hours in triplicate. RNA was then extracted for hybridization on Affymetrix microarrays. CRLF2+ patient-derived xenografts (05-412, 05-440, and 05-537) were treated in vivo for 3 days with vehicle, CHZ868, dexamethasone, or CHZ868 + dexmathasone combination for 3 days and then sacrificed. Transcriptional profiling was performed on unselected splenocytes from these animals.