title: STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia.
abstract: Large granular lymphocyte leukemia (LGL L) has been morphologically characterized as a group of lymphoproliferative diseases that include T-cell large granular lymphocytic leukemia (T-LGL L) and chronic lymphoproliferative disorders of natural killer cells (CLPD-NK). We investigated mutations in the Src homology 2 (SH2) domain of the signal transducer and activator of transcription 3 (STAT3) gene in Asian cohorts of T-LGL L and CLPD-NK (n = 42 and 11, respectively). Two mutations, Y640F and D661Y, were identified using direct sequencing or allele-specific (AS) PCR. Y640F and D661Y mutations were found in seven and 18 patients, respectively. Two patients were positive for both mutations. Frequencies of STAT3 mutations in T-LGL L and CLPD-NK were 47.6% and 27.2%, respectively. Pure red cell aplasia (PRCA) was associated with the mutations (P = 0.005). The mutations were persistently found at stable levels in some patients after more than 5 years using AS-quantitative PCR. The results of the present study indicate that the SH2 domain of the STAT3 gene is frequently mutated in Asian T-LGL L and CLPD-NK, and that PRCA is closely correlated with the mutations.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan; Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ishida
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.forename: Nodoka
authors.initials: N
authors.lastname: Sekiguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Chiaki
authors.initials: C
authors.lastname: Taira
authors.forename: Kayoko
authors.initials: K
authors.lastname: Momose
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nishina
authors.forename: Noriko
authors.initials: N
authors.lastname: Senoo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakai
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ito
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012010:Red-Cell Aplasia, Pure / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D055815:Young Adult
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Cytotoxic T cell; STAT3; large granular lymphocyte leukemia; natural killer cell; pure red cell aplasia