title: Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites.
abstract: Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.
authors.affiliation: *Department of Pathology, West China Hospital of Sichuan University, Chengdu, China †Department of Pathology, City of Hope Medical Center, Duarte, CA ‡İzmir International Biomedicine and Genome Institute (iBG-izmir) §Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Gao
authors.forename: Sha
authors.initials: S
authors.lastname: Zhao
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Liu
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Zhang
authors.forename: Gan-Di
authors.initials: GD
authors.lastname: Li
authors.forename: Can
authors.initials: C
authors.lastname: Küçük
authors.forename: Xiao-Zhou
authors.initials: XZ
authors.lastname: Hu
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Wen-Shuang
authors.initials: WS
authors.lastname: Ding
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Yan
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Yao
authors.forename: Jian Chao
authors.initials: JC
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D019675:Genes, T-Cell Receptor gamma; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human