Open AccessSTAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia
Author(s) -
Ishida Fumihiro,
Matsuda Kazuyuki,
Sekiguchi Nodoka,
Makishima Hideki,
Taira Chiaki,
Momose Kayoko,
Nishina Sayaka,
Senoo Noriko,
Sakai Hitoshi,
Ito Toshiro,
Kwong YokLam
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12341
Subject(s) - leukemia , biology , pure red cell aplasia , immunology , lymphoproliferative disorders , lymphocyte , stat protein , microbiology and biotechnology , gene , cancer research , lymphoma , stat3 , genetics , bone marrow
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 ( SH 2) domain of the signal transducer and activator of transcription 3 ( STAT 3) 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 SH 2 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.