IGH rod-like tracer: An AlphaFold2 structural similarity extraction-based predictive biomarker for MRD monitoring in pre-B-ALL

Zhongling Zhuo; Qingchen Wang; Chang Li; Lili Zhang; Lanxin Zhang; Ran You; Yan Gong; Ying Hua; Linzi Miao; Jiefei Bai; Chunli Zhang; Ru Feng; Meng Chen; Fei Su; Chenxue Qu; Fei Xiao

iScience (Jul 2023)

IGH rod-like tracer: An AlphaFold2 structural similarity extraction-based predictive biomarker for MRD monitoring in pre-B-ALL

Zhongling Zhuo,
Qingchen Wang,
Chang Li,
Lili Zhang,
Lanxin Zhang,
Ran You,
Yan Gong,
Ying Hua,
Linzi Miao,
Jiefei Bai,
Chunli Zhang,
Ru Feng,
Meng Chen,
Fei Su,
Chenxue Qu,
Fei Xiao

Affiliations

Zhongling Zhuo: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Department of Laboratory Medicine, Peking University People’s Hospital, Beijing, China
Qingchen Wang: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
Chang Li: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Lili Zhang: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Lanxin Zhang: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Ran You: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
Yan Gong: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
Ying Hua: Department of Pediatrics, Peking University First Hospital, Beijing, China
Linzi Miao: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
Jiefei Bai: Department of Hematology, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Chunli Zhang: Department of Hematology, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Ru Feng: Department of Hematology, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Meng Chen: National Cancer Data Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
Fei Su: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Chenxue Qu: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China; Corresponding author
Fei Xiao: Clinical Biobank, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Corresponding author

Journal volume & issue: Vol. 26, no. 7
p. 107107

Abstract

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Summary: Sequence variation resulting from the evolution of IGH clones and immunophenotypic drift makes it difficult to track abnormal B cells in children with precursor B cell acute lymphoblastic leukemia (pre-B-ALL) by flow cytometry, qPCR, or next-generation sequencing (NGS). The V-(D)-J regions of immunoglobulin and T cell receptor of 47 pre-B-ALL samples were sequenced using the Illumina NovaSeq platform. The IGH rod-like tracer consensus sequence was extracted based on its rod-like alpha-helices structural similarity predicted by AlphaFold2. Additional data from published 203 pre-B-ALL samples were applied for validation. NGS-IGH (+) patients with pre-B-ALL had a poor prognosis. Consistent CDR3-coded protein structures in NGS-IGH (+) samples could be extracted as a potential follow-up marker for pre-B-ALL children during treatment. IGH rod-like tracer from quantitative immune repertoire sequencing may serve as a class of biomarker with significant predictive values for the dynamic monitoring of MRD in pre-B-ALL children.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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