Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes

Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm sporadically affecting people from Asia and Central and South America. The median overall survival (OS) is less than 2 months, irrespective of treatments. Epstein-Barr virus (EBV) is mostly detected in the leukemia cells and is proposed to contribute to the pathogenesis of ANKL 1 , 2 , 3 . ANKL represents a distinct disease entity within the continuous spectrum of EBV-associated T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs). Patients with ANKL usually manifest a fulminant and extremely aggressive clinical course. However, some clinicopathologic features may be shared with different types of EBV-T/NK-LPDs, which leads to the occurrence of a few cases with features intermediate between two similar disorders 4 , 5 , 6 . The diagnosis of ANKL largely relies on the identification of morphologically and immunophenotypically aberrant leukemia cells 7 . Chromosomal gains and losses, activating STAT3 and STAT5 mutations, and HACE1 hypermethylation have only been sporadically detected 8 , 9 , 10 . Moreover, optimal therapy of ANKL has not yet been established 11 . To date, less than 350 cases of ANKL have been described in English literature worldwide. Because of the rarity of ANKL, the clinical features, potential pathogenesis, therapeutic strategies, and prognostic factors still lack in understanding. A multicenter study is critically needed for better understanding of this disease.