Dr. Mesa on Ruxolitinib in Chronic Myeloid Leukemia

Ruben A. Mesa, MD, Professor of Medicine, Division of Hematology & Medical Oncology, Mayo Clinic, discusses the mechanism of action of ruxolitinib and interest in JAK1/2 inhibition in patients with chronic myeloid leukemia (CML).

Ruxolitinib is an inhibitor of JAK1 and JAK2 but it is not specific to these mutations, unlike the TKIs currently available to treat CML, which are targeted to BCR-ABL. This attribute makes the agent a potentially unique treatment in CML.

Treatment with ruxolitinib seems to impact JAK2 V617F allele burden. Overall, Mesa says, V617F is a point mutation and currently there is not a sythesized molecule that is specific to this mutation. However, Mesa notes, researchers believe the upregulation of JAK2, whether through the V617F mutation or another mutation, is a key target and its inhibition provides benefit. As a result, there are several trials looking at combinations that target pathways upstream or downstream of JAK2, including treatment with PI3K and mTOR inhibitors.