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Ann Lab Med. 2019 Mar;39(2):125-132. doi: 10.3343/alm.2019.39.2.125.

T-Cell Receptor Rearrangements Determined Using Fragment Analysis in Patients With T-Acute Lymphoblastic Leukemia.

Author information

1
Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea.
2
Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea. iskim0710@gmail.com.
3
Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea. cchl@pusan.ac.kr.
4
Hematologic Malignancies Branch, National Cancer Center, Goyang, Korea.
5
Department of Pediatrics, Pusan National University School of Medicine, Busan, Korea.
6
Department of Pediatrics, Kosin University College of Medicine, Busan, Korea.
7
Green Cross Genome, Yongin, Korea.
8
Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Korea.
9
Center for Pediatric Oncology, National Cancer Center, Goyang, Korea.
10
Hematologic Oncology Clinic, Center for Specific Organs Cancer Research Institute & Hospital, National Cancer Center, Goyang, Korea.
#
Contributed equally

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:

Clonality; Fragment analysis; Minimal residual disease; T-acute lymphoblastic leukemia; T-cell receptor

PMID:
30430774
PMCID:
PMC6240512
DOI:
10.3343/alm.2019.39.2.125
[Indexed for MEDLINE]
Free PMC Article

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