Patients with clinical characteristics of chronic myelogenous leukemia (CML) lacking a BCR/ABL fusion gene are usually referred to as having atypical CML. Most commonly, diverse tyrosine kinase genes such as the receptors FGFR1, PDGFRA, or PDGFRB are involved. In addition, the Janus (tyrosine) kinases (JAK) can be deregulated in leukemia/lymphoma by copy number alterations, mutations and chromosomal translocations.
Chromosomal translocations targeting JAK2 are rare but recurrent abnormalities in myeloproliferative neoplasms, acute myeloid leukemia, acute lymphoblastic leukemia and lymphoma. In cell line models and primary patient material, it could be shown that treatment with ruxolitinib has significant activity against JAK2 activated by gene rearrangement and presents evidence for potential activity against cells with JAK2 amplification.
Clinical Applications
- Chronic Myelogenous Leukemia and Myeloproliferative Neoplasms (CML/MPN)
- Acute Myelogenous Leukemia (AML)
- Acute Lymphoblastic Leukemia (ALL)