AGGRESSIVE NK CELL LEUKEMIA: CLONALITY, CLINICAL AND GENETIC FEATURES

Introduction: Aggressive natural killer cell leukemia (ANKL) is an extraordinary rare aggressive malignancy of NK cells, but is relatively common in Asian. The accurate diagnosis of ANKL remains a great challenge. This study intends to describe the clonality, clinical and genetic features of ANKL and guide the diagnosis of this disease. Methods: A total of 45 consecutive newly diagnosed ANKL patients were recruited from the First Affiliated Hospital of Nanjing Medical University, and clinical data were collected. Cytological morphology, flow cytometric analysis including killer cell immunoglobulin-like receptors (KIR), karyotypic analysis and molecular biology tests were used to diagnose and assess the monotypic clonality of NK cells. Survival analyses were done to verify the prognostic predictors of ANKL. Results: All patients were adults, with a median age of 39 years (range 8-80 years) and a male: female ratio 1.4:1 (Table 1). B symptoms and fever were noted in all patients. Splenomegaly (91.1%) and hemophagocytic lymphohistiocytosis (HLH) (80.0%) were also common. Most patients (34/38) were confirmed with EBV infection. Immunophenotyping of the ANKL cells were typically positive for CD2 and CD3, and CD7, CD16 and CD56 were positive for 66.7%, 52.9% and 87.8%, respectively. Either monotypic (n=8) or complete lack (n=20) of KIR expression was observed in 28 ANKL patients (Figure 1). Highly complex karyotypes were detected in five cases. No patient had clonal rearrangement of the T-cell receptor gene, and only one patient had STAT3 mutation. Median overall survival of ANKL patients was 27 days. HLH (P<0.001), pleural effusion/ascites (P=0.003), absolute lymphocyte count ≤4.0×109/L (P<0.001), neutropenia (P=0.001), thrombocytopenia (P=0.009), positive EBV-DNA (P=0.036), positive CD56 (P=0.035), and performance status >2 (P<0.001) were identified as unfavorable factors of early death. Conclusions: Our findings suggest that ANKL is a highly aggressive leukemia with high mortality. Detection of immunophenotyping and KIR may have important diagnostic value. More studies are needed to obtain a better understanding of the pathogenesis of this disease. Complete lack of KIR antigens was observed in ANKL patient 20. The expression of KIR was evaluated by gating on the total population of CD3– and CD56+ NK cells. Keywords: Epstein-Barr virus (EBV); non-Hodgkin lymphoma (NHL).