Acute promyelocytic leukemia with JAK2 V617F and severe differentiation syndrome

Leuk Res Rep. 2014 Dec 25;4(1):8-11. doi: 10.1016/j.lrr.2014.12.003. eCollection 2015.


Myeloproliferative neoplasms transformed into AML usually have a poor prognosis. We report a case of essential thrombocythemia with myelofibrosis that transformed into acute promyelocytic leukemia (APL) with both the t(15;17) translocation as well as the JAK2 V617F mutation. Clinically, this case was notable for severe differentiation syndrome despite treatment with high-dose dexamethasone. Cytokine production by differentiating APL cells was not directly abrogated by JAK2 inhibitors in vitro, suggesting that JAK2 V617F enhances the hyperinflammatory response downstream of cytokines. JAK1/2 inhibitors may therefore dampen the inflammatory cascade downstream of cytokine production, similar to glucocorticoids, and have a role in treating severe differentiation syndrome.

Keywords: Acute promyelocytic leukemia (APL); Differentiation syndrome; Essential thrombocythemia (ET); JAK2; Myeloproliferative neoplasm (MPN).