Ann Lab Med 2017; 37(4): 331-335
Detection of Immunoglobulin Heavy Chain Gene Clonality by Next-Generation Sequencing for Minimal Residual Disease Monitoring in B-Lymphoblastic Leukemia
Saeam Shin, M.D.1,2,*, In Sik Hwang, M.S.3,*, Jieun Kim, M.D.1, Kyung-A Lee, M.D.1, Seung-Tae Lee, M.D.1, and Jong Rak Choi, M.D.1
Department of Laboratory Medicine1, Yonsei University College of Medicine, Seoul; Department of Laboratory Medicine2, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul; Brain Korea 21 PLUS Project for Medical Science3, Yonsei University, Seoul, Korea
Correspondence to: Seung-Tae Lee
Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Tel: +82-2-2228-2450
Fax: +82-2-364-1583
Co-corresponding author: Jong Rak Choi
Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Tel: +82-2-2228-2441
Fax: +82-2-364-1583
* These authors contributed equally to this work.
Received: November 8, 2016; Revised: January 3, 2017; Accepted: March 29, 2017; Published online: July 1, 2017.
© The 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 ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Minimal residual disease (MRD) following B-lymphoblastic leukemia (B-ALL) treatment has gained prognostic importance. Clonal immunoglobulin heavy chain (IGH) gene rearrangement is a useful follow-up marker in B-ALL owing to its high positivity rate. We evaluated the performance and clinical applicability of a next-generation sequencing (NGS) assay for IGH rearrangement in B-ALL MRD monitoring. IGH rearrangement was tested by using fluorescence PCR-fragment analysis and the NGS assay in eight B-ALL patients. The NGS assay was run on two platforms: the Ion Torrent PGM (Thermo Fisher Scientific, USA) (18 samples from 1st to 7th patients) and the MiSeq system (Illumina, USA) (four samples from 8th patient). All initial diagnostic samples and four follow-up samples were positive for clonal IGH rearrangement with fluorescence PCR-fragment analysis and the NGS assay, and six follow-up samples were positive only with NGS. In one case with BCR-ABL1 translocation, BCR-ABL1 quantitative PCR was negative but the NGS IGH assay was positive just prior to full-blown relapse, suggesting the high sensitivity and clinical utility of the NGS assay. The NGS assay is proposed for MRD monitoring in B-ALL Additional studies are needed to confirm the clinical implications of cases showing positive results only in NGS.
Keywords: Immunoglobulin heavy chain gene rearrangement, Minimal residual disease, B-lymphoblastic leukemia, Next-generation sequencing

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