FERM Target for Rare Leukemia

November 18, 2011 | Melissa Marino

Most patients diagnosed with adult T-cell leukemia/lymphoma (ATLL) – a rare, aggressive blood cancer – will die within a year of diagnosis. No currently available treatments alter the disease’s aggressive clinical course.

Utpal Davé, M.D., and colleagues are working to identify genes and pathways that drive or initiate ATLL. In the Oct. 6 issue of Blood, they report that JAK3 (a component of the IL-2 signaling pathway) may be a therapeutic target for this disease. Among 36 ATLL patients, Davé and colleagues identified four patients with mutations in the “FERM” domain of JAK3, which promoted activity of the enzyme and the downstream pathways that regulate cell growth. They also showed that cells containing mutant JAK3 were more sensitive to an existing JAK3 inhibitor (tofacitinib, which is currently in clinical trials for autoimmune disorders) than cells with wild-type JAK3.

The results underscore the importance of this pathway in ATLL and suggest that JAK3 may represent an important therapeutic target for this aggressive disease.

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