Acute promyelocytic leukemia with JAK2 V617F and severe differentiation syndrome

•Case of essential thrombocythemia transformed to acute promyelocytic leukemia.•Leukemia cells contained both t(15;17) and JAK2 V617F mutation.•Severe differentiation syndrome in response to ATRA, possibly related to JAK2 V617F.•JAK1/2 inhibitors may have clinical utility in differentiation syndrome.

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.