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Gene mutation profiles and prognostic implications in Korean patients with T-lymphoblastic leukemia

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Abstract

Genetic alterations implicated in the leukemogenesis 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 cytogenetic 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 profile 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 implication of NOTCH1 mutations in adult T-ALL.

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Acknowledgments

This work was supported by a grant #CB08121 from the IN-SUNG Foundation for Medical Research at Samsung Medical Center, Seoul.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Hee Jae Huh, Sun-Hee Kim & Hee-Jin Kim

  2. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Soo Hyun Lee, Keon Hee Yoo, Ki Woong Sung & Hong Hoe Koo

  3. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Jun Ho Jang, Kihyun Kim, Seok Jin Kim, Won Seog Kim & Chul Won Jung

  4. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, South Korea

    Ki-O Lee

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Supplementary Table 1

Primer sequences for PCR and sequencing experiments (DOCX 56.4 kb)

Supplementary Fig. 1

Survival analyses by Kaplan–Meier estimates of overall survival (OS) and event-free survival (EFS) according to the FBXW7 mutation status in pediatric T-ALL patients (upper panels, a and b) and in adult T-ALL patients (lower panels, c and d) (DOCX 119 kb)

Supplementary Fig. 2

Survival analyses by Kaplan–Meier estimates of overall survival (OS) and event-free survival (EFS) according to the PHF6 mutation status in pediatric T-ALL patients (upper panels, a and b) and in adult T-ALL patients (lower panels, c and d) (DOCX 117 kb)

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Huh, H.J., Lee, S.H., Yoo, K.H. et al. Gene mutation profiles and prognostic implications in Korean patients with T-lymphoblastic leukemia. Ann Hematol 92, 635–644 (2013). https://doi.org/10.1007/s00277-012-1664-2

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