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Clin Chim Acta. 2019 Jan;488:81-89. doi: 10.1016/j.cca.2018.10.037. Epub 2018 Oct 31.

Considerations for monitoring minimal residual disease using immunoglobulin clonality in patients with precursor B-cell lymphoblastic leukemia.

Author information

1
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, South Korea.
2
Department of Pediatrics, College of Medicine, The Catholic University of Korea, South Korea.
3
Department of Hematology, Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, South Korea.
4
Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, South Korea.
5
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, South Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, South Korea.
6
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, South Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, South Korea. Electronic address: yonggoo@catholic.ac.krand.
7
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, South Korea; Catholic Genetic Laboratory Center, College of Medicine, The Catholic University of Korea, South Korea. Electronic address: microkim@catholic.ac.kr.

Abstract

BACKGROUND:

Minimal residual disease (MRD) monitoring is a powerful tool to predict the risk of relapse. Herein, we present an MRD monitoring strategy for B-cell lymphoblastic leukemia (B-ALL) using high-throughput sequencing (HTS) of immunoglobulin (Ig) clonality before implementation into routine practice.

METHODS:

We selected 74 bone marrow (BM) specimens from 47 patients who were diagnosed with B-ALL. Ig clonality was analyzed using both fragment analysis and HTS. The performance of Ig clonality was evaluated through comparison of the results from real-time quantitative polymerase chain reaction (qPCR) of leukemia-specific fusion transcripts and flow cytometry.

RESULTS:

IGH clonality was observed in all patients, and the sum of clonal burden varied (9.47%-96.77%). IGK clonality was identified in 70% of patients and availed in cases with low IGH clonal burden. The total IGH clonal burden was significantly correlated with the proportion of leukemic blasts, leukemia-specific fusion transcripts, and flow cytometry. We recognized the different responses of each clone and emerging clones originating from the trace of Ig rearrangement presented in the initial specimen. IGH clonal burden after chemotherapy represented patient outcomes well. IGH assay also provided information of repertoire diversity of IGH rearrangement.

CONCLUSION:

The Ig clonality assay via HTS will be a promising tool for MRD monitoring of B-ALL through an adequate strategy to identify and monitor individual clones and determine repertoire diversity.

KEYWORDS:

B-cell lymphoblastic leukemia; High-throughput sequencing; Immunoglobulin clonality; Minimal residual disease; Repertoire

PMID:
30389459
DOI:
10.1016/j.cca.2018.10.037
[Indexed for MEDLINE]

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