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Circulating tumor DNA: clinical roles in diffuse large B cell lymphoma

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Abstract

Diffuse large B cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma (NHL), is a clinically and molecularly heterogeneous malignant lymphoproliferative disease. In the era of personalized medicine, genetic information is critical to early diagnosis, aiding risk stratification, directing therapeutic option, and monitoring disease relapse. However, lacking a circulating disease with most DLBCL cases hampers the acquisition of tumor genomic landscapes and disease dynamics. Circulating tumor DNA (ctDNA) is a novel noninvasive, real-time, and tumor-specific biomarker, reliably reflecting the comprehensive tumor genetic profiles, thus holds great promise in individualized medicine, including precise diagnosis and prognosis, response monitoring, and relapse detection of DLBCL. Here, we reviewed the recent advances of ctDNA in DLBCL and discussed its clinical values at different time points during the disease courses by comparing with the current routine methods in clinical practice. Collectively, we anticipated that ctDNA will ultimately be integrated into the management of DLBCL to facilitate precision medicine.

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Abbreviations

AF:

allele frequency

CAPP-Seq:

cancer personalized profiling by deep sequencing

cfDNA:

cell-free DNA

CLL:

chronic lymphocytic leukemia

CMR:

complete molecular remission

COO:

cell of origin

CR:

complete response

CSF:

cerebrospinal fluid

ctDNA:

circulating tumor DNA

DLBCL:

diffuse large B cell lymphoma

dPCR:

digital polymerase chain reaction

EMA:

European Medicines Agency

GEP:

gene expression profiling

FL:

follicular lymphoma

HL:

Hodgkin lymphoma

HSCT:

allogeneic stem cell transplantation

HTS:

high-throughput sequencing

Ig:

immunoglobulin

IgCap:

capturing and sequencing the IgH gene

IgH:

immunoglobulin heavy chain

IPI:

International Prognostic Index

LDH:

serum lactate dehydrogenase

MCL:

mantle cell lymphoma

MRD:

minimal residual disease

MTV:

metabolic tumor volume

MYD88:

myeloid differentiation primary response gene

NCI:

National Cancer Institute

NCCN:

National Comprehensive Cancer Network

NGS:

next-generation sequencing

NHL:

non-Hodgkin lymphoma

NPV:

negative predictive value

NSCLC:

non-small-cell lung cancer

OS:

overall survival

PCNSL:

primary central nerve system lymphoma

PCR:

polymerase chain reaction

PET/CT:

18-fluoro-deoxyglucose positron emission tomography combined with CT

PFS:

progression-free survival

PPV:

positive predictive value

REAL:

the Revised European American Classification

rrDLBCL:

refractory/relapse DLBCL

RS:

Richter’s syndrome

SINE:

selective inhibitors of nuclear export

SUV:

single nucleotide variant

tFL:

transforming follicular lymphoma

WES:

whole exome sequencing

WHO:

the World Health Organization

XPO1:

exportin-1

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Funding

This study was supported by National Natural Science Foundation of China (81170485, 81170488, 81370657, and 81470328), Key Projects of the Health Department of Jiangsu Province (K201108), Jiangsu Province’s Medical Elite Programme (RC2011169), the National Public Health Grand Research Foundation (201202017), a project funded by the Priority Academic Programme Development of Jiangsu Higher Education Institute (JX10231801), Project of National Key Clinical Specialty, the National Science & Technology Pillar Programme (2014BAI09B12), and a project funded by Jiangsu Provincial Special Programme of Medical Science (BL2014086).

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

    Fang-Tian Wu, Luo Lu, Wei Xu & Jian-Yong Li

  2. Key Laboratory of Hematology of Nanjing Medical University, Nanjing, 210029, China

    Fang-Tian Wu, Luo Lu, Wei Xu & Jian-Yong Li

  3. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China

    Fang-Tian Wu, Luo Lu, Wei Xu & Jian-Yong Li

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  1. Fang-Tian Wu
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  2. Luo Lu
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  3. Wei Xu
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  4. Jian-Yong Li
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F-T W and L L searched the literature and drafted the manuscript. All authors read, revised, and approved the final manuscript.

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Correspondence to Wei Xu or Jian-Yong Li.

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Wu, FT., Lu, L., Xu, W. et al. Circulating tumor DNA: clinical roles in diffuse large B cell lymphoma. Ann Hematol 98, 255–269 (2019). https://doi.org/10.1007/s00277-018-3529-9

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  • DOI: https://doi.org/10.1007/s00277-018-3529-9

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