| First Author | Wu SC | Year | 2015 |
| Journal | Cancer Cell | Volume | 28 |
| Issue | 1 | Pages | 29-41 |
| PubMed ID | 26175414 | Mgi Jnum | J:222994 |
| Mgi Id | MGI:5646311 | Doi | 10.1016/j.ccell.2015.06.005 |
| Citation | Wu SC, et al. (2015) Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell 28(1):29-41 |
| abstractText | A variety of cancers depend on JAK2 signaling, including the high-risk subset of B cell acute lymphoblastic leukemias (B-ALLs) with CRLF2 rearrangements. Type I JAK2 inhibitors induce paradoxical JAK2 hyperphosphorylation in these leukemias and have limited activity. To improve the efficacy of JAK2 inhibition in B-ALL, we developed the type II inhibitor CHZ868, which stabilizes JAK2 in an inactive conformation. CHZ868 potently suppressed the growth of CRLF2-rearranged human B-ALL cells, abrogated JAK2 signaling, and improved survival in mice with human or murine B-ALL. CHZ868 and dexamethasone synergistically induced apoptosis in JAK2-dependent B-ALLs and further improved in vivo survival compared to CHZ868 alone. These data support the testing of type II JAK2 inhibition in patients with JAK2-dependent leukemias and other disorders. |
