Flow Cytometric Immunophenotyping Is Sensitive for the Early Diagnosis of De Novo Aggressive Natural Killer Cell Leukemia (ANKL): A Multicenter Retrospective Analysis

PLoS One. 2016 Aug 2;11(8):e0158827. doi: 10.1371/journal.pone.0158827. eCollection 2016.


Aggressive natural killer cell leukemia (ANKL) is a fatal hematological neoplasm characterized by a fulminating clinical course and extremely high mortality. Current diagnosis of this disease is not effective during the early stages and it is easily misdiagnosed as other NK cell disorders. We retrospectively analyzed the clinical characteristics and flow cytometric immunophenotype of 47 patients with ANKL. Patients with extranodal NK/T cell lymphoma, nasal type (ENKTL) and chronic lymphoproliferative disorder of NK cell (CLPD-NK), who were diagnosed during the same time period were used for comparisons. Abnormal NK cells in ANKL were found to have a distinctiveCD56bright/CD16dim immunophenotype and markedly increased Ki-67 expression, whereas CD57 negativity and reduced expression of killer immunoglobulin-like receptor (KIR), CD161, CD7, CD8 and perforin were exhibited compared with other NK cell proliferative disorders (p<0.05). The positive rates of flow cytometry detection (97.4%) was higher than those of cytomorphological (89.5%), immunohistochemical (90%), cytogenetic (56.5%) and F-18 fluorodeoxyglucose positron emission tomography/computer tomography (18-FDG-PET/CT) examinations (50%) (p<0.05). ANKL is a highly aggressive leukemia with high mortality. Flow cytometry detection is sensitive for the early and differential diagnosis of ANKL with high specificity.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / immunology
  • Bone Marrow / pathology*
  • Cytogenetic Analysis
  • Diagnosis, Differential
  • Early Detection of Cancer
  • Female
  • Flow Cytometry / methods*
  • Humans
  • Immunophenotyping / methods*
  • Karyotype
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology*
  • Leukemia, Large Granular Lymphocytic / diagnosis*
  • Leukemia, Large Granular Lymphocytic / genetics
  • Leukemia, Large Granular Lymphocytic / immunology
  • Leukemia, Large Granular Lymphocytic / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Young Adult

Grants and funding

This study was supported by the National Natural Science Foundation of China (NSFC 81300390).