ORIGINAL ARTICLE Gene mutation profiles and prognostic implications in Korean patients with T-lymphoblastic leukemia Hee Jae Huh & Soo Hyun Lee & Keon Hee Yoo & Ki Woong Sung & Hong Hoe Koo & Jun Ho Jang & Kihyun Kim & Seok Jin Kim & Won Seog Kim & Chul Won Jung & Ki-O Lee & Sun-Hee Kim & Hee-Jin Kim Received: 5 September 2012 / Accepted: 17 December 2012 / Published online: 25 January 2013 # Springer-Verlag Berlin Heidelberg 2013 Abstract Genetic alterations implicated in the leukemogene- sis of T cell acute lymphoblastic leukemia (T-ALL) have been identified in recent years. In this study, we investigated gene mutation profiles and prognostic implications in a series of Korean T-ALL patients. The study patients were 29 Korean patients with T-ALL; 13 adults (45 %) and 16 children (55 %; male-to-female ratio, 25:4). Clinical, hematologic, and cytoge- netic findings were reviewed. We performed mutation analyses for NOTCH1, FBXW7, PHF6, and IL7R genes and survival analyses according to the mutational status. Gene mutations were identified in 66 % of the patients in our series (19/29). Eighteen patients (62 %) had NOTCH1/FBXW7 mutations. Sixteen patients (55 %) had NOTCH1 mutations including nine novel mutations, and eight patients (28 %) had known FBXW7 mutations. Eight patients (28 %; six males and two females) had PHF6 mutations including four novel mutations. Three patients (10 %) had IL7R mutations, which were all novel in- frame insertion or deletion–insertions. The gene mutation pro- file combined with cytogenetics and FISH study for the p16 gene detected genetic aberrations in 90 % of patients (26/29). There was no significant difference in the frequency of gene mutations between the pediatric and adult patients with T-ALL. Survival analyses suggested a favorable prognostic implication of NOTCH1 mutations in adult T-ALL. Gene mutation studies for NOTCH1, FBXW7, PHF6, and IL7R could detect genetic alterations in a majority of Korean T-ALL patients with novel mutations. We observed similar mutation profiles between adult and pediatric T-ALL, and a favorable prognostic impli- cation of NOTCH1 mutations in adult T-ALL. Keywords T cell acute lymphoblastic leukemia . NOTCH1 . Gene . Mutation . Survival . Korea Introduction T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy in which multiple genetic defects collaborate in the transformation of T cell progenitors. It accounts for 15 and 25 % of newly diagnosed ALL cases in children and adults, respectively [1, 2]. T-ALL is generally characterized by high circulating blast cell counts, mediastinal masses, and central nervous system involvement. Although the outcomes of T- ALL have improved in recent decades with current intensive therapy and hematopoietic stem cell transplantation, about 10 % of childhood and 37 % of adult T-ALL patients relapse [3, 4]. It is likely that further improvements in treatment out- comes will require a comprehensive understanding of the ge- netic alterations contributing to leukemogenesis [5]. T-ALL is a genetically heterogeneous disease comprising several clinico- biological entities. Malignant transformation of T cells is caused by chromosomal translocation and other genetic and Electronic supplementary material The online version of this article (doi:10.1007/s00277-012-1664-2) contains supplementary material, which is available to authorized users. H. J. Huh : S.-H. Kim : H.-J. Kim (*) Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea e-mail: heejinkim@skku.edu S. H. Lee : K. H. Yoo : K. W. Sung : H. H. Koo Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea J. H. Jang : K. Kim : S. J. Kim : W. S. Kim : C. W. Jung Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea K.-O. Lee Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea Ann Hematol (2013) 92:635–644 DOI 10.1007/s00277-012-1664-2