Ann Lab Med 2019; 39(2): 125-132  https://doi.org/10.3343/alm.2019.39.2.125
T-Cell Receptor Rearrangements Determined Using Fragment Analysis in Patients With T-Acute Lymphoblastic Leukemia
Hyerim Kim, M.D.1, In-Suk Kim, M.D.2*, Chulhun L. Chang, M.D.2*, Sun-Young Kong, M.D.3, Young Tak Lim, M.D.4, Seom Gim Kong, M.D.5, Eun Hae Cho, M.D.6, Eun-Yup Lee, M.D.1, Ho-Jin Shin, M.D.7, Hyeon Jin Park, M.D.8, Hyeon-Seok Eom, M.D.9, and Hyewon Lee, M.D.9
1Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea; 2Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea; 3Hematologic Malignancies Branch, National Cancer Center, Goyang, Korea; 4Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea; 5Department of Pediatrics, Kosin University College of Medicine, Busan, Korea; 6Green Cross Genome, Yongin, Korea; 7Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea; 8Center for Pediatric Oncology, National Cancer Center, Goyang, Korea; 9Hematologic Oncology Clinic, Center for Specific Organs Cancer Research Institute & Hospital, National Cancer Center, Goyang, Korea
Corresponding author: In-Suk Kim, M.D. https://orcid.org/0000-0002-7243-9173
Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea
Tel: +82-55-360-1878
Fax: +82-55-360-1880
E-mail: iskim0710@gmail.com
Chulhun L. Chang, M.D. https://orcid.org/0000-0001-9117-4919
Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea
Tel: +82-55-360-1877
Fax: +82-55-360-1880
E-mail: cchl@pusan.ac.kr
*These two authors contributed equally to this work.
Received: August 20, 2017; Revised: April 23, 2018; Accepted: September 2, 2018; Published online: March 1, 2019.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Chromosomal abnormalities and common genetic rearrangements related to T-acute lymphoblastic leukemia (T-ALL) are not clear. We investigated T-cell receptor (TCR) rearrangement in Korean T-ALL patients by fragment analysis, examining frequency, association between clinicopathologic characteristics and TCR clonality, and feasibility for detecting minimal residual disease (MRD).
Methods: In 51 Korean patients diagnosed as having T-ALL, TCR rearrangement was analyzed using the IdentiClone TCR gene clonality assay (InVivoScribe Technologies, San Diego, CA, USA) from archived bone marrow specimens. Limit of detection (LOD) and clonal stability at relapse were evaluated. The association between clinical prognosis and TCR clonality was examind by age and immunophenotypic classification.
Results: Thirty-eight patients (74.5%) had 62 clonal products of TCRβ, TCRγ, and/or TCRδ rearrangements at diagnosis. Children with T-ALL (<12 years) showed a higher frequency of clonality (93.8%) than adolescents/adults (65.7%; ≥12 years). Patients with a mature immunophenotype (84.4%) showed a relatively higher frequency of clonality than those with the immature immunophenotype (57.9%). Survival and event-free survival were not influenced by immunophenotype or TCR clonality. The LOD was 1%. Clonal evolution at the relapse period was noted.
Conclusions: The overall detection rate of TCR clonality was 74.5%. Survival did not differ by TCR clonality or immunophenotype and age group. Fragment analysis of TCR rearrangement cannot be used to assess MRD due to low sensitivity. Further research on the relationship between prognosis and frequency of TCR rearrangements is needed, using more sensitive methods to detect clonality and monitor MRD.
Keywords: T-acute lymphoblastic leukemia, T-cell receptor, Clonality, Minimal residual disease, Fragment analysis



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