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Telomere length and somatic mutations in correlation with response to immunosuppressive treatment in aplastic anaemia
Author(s) -
Park Hee S.,
Park Si N.,
Im Kyongok,
Kim SungMin,
Kim JungAh,
Hwang Sang M.,
Lee Dong S.
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14691
Subject(s) - telomere , somatic evolution in cancer , somatic cell , biology , fluorescence in situ hybridization , bone marrow , medicine , aplastic anemia , haematopoiesis , cytogenetics , gastroenterology , immunology , microbiology and biotechnology , oncology , gene , genetics , stem cell , chromosome
Summary We investigated the frequencies of cytogenetic aberrations and somatic mutations of prognostic relevance in 393 patients with aplastic anaemia ( AA ). Clonality was determined by G‐banding/fluorescence in situ hybridization ( FISH ) ( n = 245), and targeted capture sequencing was performed for 88 haematopoiesis‐related genes ( n = 70). The telomere length ( TL ) of bone marrow nucleated cells was measured at the single cell level by FISH ( n = 135). Eighteen (4·6%) patients showed disease progression, and monosomy 7 (50·0%) was the most predominant cytogenetic evolution at disease transformation. One third of patients (32·9%) presented at least 1 mutation; the most frequently mutated genes were NOTCH 1, NF 1, SCRIB , BCOR and DNMT 3A . The patient group with clonal changes (30·7%) showed an adverse response to immunosuppressive treatment ( IST ), compared to the non‐clonal group, but this finding did not show statistical significance. The TL of AA patients was significantly shorter than normal control and patients with clonal changes showed significantly shorter TL s. Patients with TL >5·9 showed a higher response rate to IST ( P = 0·048). In conclusion, the patients with clonal changes or TL attrition showed a poor response to IST . Shorter TL can be used not only as a biomarker, but also as a predictive marker for treatment response to IST .