Elevated serum granulysin and its clinical relevance in mature NK-cell neoplasms.
Mature natural killer (NK)-cell neoplasms include extranodal NK/T cell lymphoma, nasal type (ENKL), aggressive NK-cell leukemia (ANKL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK). Granulysin, a cytolytic granule protein, is expressed in cytotoxic T cells and NK cells, and is found in the sera as well, and functions as a cytotoxic and proinflammatory protein. Cytolytic proteins, such as granzyme B and perforin, have been shown to play crucial pathophysiological roles in NK/T cell neoplasms and have also been utilized for diagnostic purposes. Granulysin in NK-cell proliferative disorders, however, has yet to be fully analyzed. To elucidate the clinical relevance of granulysin in mature NK-cell neoplasms, we measured serum granulysin and analyzed cytolytic molecules immunohistologically. The median concentrations of serum granulysin were 39.0, 2.85, 2.8 and 1.35 ng/ml in ANKL, ENKL, CLPD-NK and healthy subjects, respectively (P < 0.01). Serum granulysin was significantly elevated in patients with ANKL compared with the levels in ENKL (P = 0.006) and CLPD-NK (P = 0.037). Furthermore, serum granulysin was correlated with whole-blood EBV viral load in ENKL and ANKL (P = 0.005) and was significantly reduced after treatment. Different expression patterns of cytolytic granule proteins were observed among the mature NK-cell neoplasms. Granulysin is closely associated with the characteristics of NK-cell neoplasms and serum granulysin may serve as a novel biomarker for these disorders.
Division of Hematology, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Nodoka
N
Sekiguchi
Naoko
N
Asano
Toshiro
T
Ito
Kayoko
K
Momose
Masanobu
M
Momose
Fumihiro
F
Ishida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural; D007945:Leukemia, Lymphoid / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D054391:Lymphoma, Extranodal NK-T-Cell / Q000097:blood* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; C075005:GNLY protein, human; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C067169:RPL22 protein, human