Aggressive natural killer leukemia (ANKL) is a proliferation of mature natural killer (NK) cells. It is very rare (fewer than 350 cases reported in the literature), with most cases described in young and middle-aged persons from China, Japan, and South America.

ANKL is almost always associated with Epstein-Barr virus (EBV) infection. Hemophagocytic lymphohistiocytosis (HLH) is reported in 60% of cases.

The main sites of involvement include the liver and spleen, the bone marrow and peripheral blood, and, less frequently, the nose and skin. Clinically, these patients commonly present with fever and liver dysfunction with a rapidly progressive course.

ANKL has high mortality (median length of survival is approximately 8 weeks).