Clinical Application of Liquid Biopsy in Non-Hodgkin Lymphoma

Abstract

Non-Hodgkin lymphoma (NHL) is a common type of hematological malignant tumor, composed of multiple subtypes that originate from B lymphocytes, T lymphocytes, and natural killer cells. A diagnosis of NHL depends on the results of a pathology examination, which requires an invasive tissue biopsy. However, due to their invasive nature, tissue biopsies have many limitations in clinical applications, especially in terms of evaluating the therapeutic response and monitoring tumor progression. To overcome these limitations of traditional tissue biopsies, a technique known as “liquid biopsies” (LBs) was proposed. LBs refer to noninvasive examinations that can provide biological tumor data for analysis. Many studies have shown that LBs can be broadly applied to the diagnosis, treatment, prognosis, and monitoring of NHL. This article will briefly review various LB methods that aim to improve NHL management, including the evaluation of cell-free DNA/circulating tumor DNA, microRNA, and tumor-derived exosomes extracted from peripheral blood in NHL.

Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

“…DLBCL is an aggressive and heterogeneous lymphoma, and studies have shown that cfDNA may have a position in the diagnosis of the disease. Various reports have shown a higher amount of cfDNA in patients with this lymphoma compared to healthy patients, a decrease in the amount of cfDNA when the treatment is effective, and a correlation between quantification of cfDNA and adverse prognosis of the disease [16,[96][97][98][99].…”

“…Shin et al designed a panel of 66 genes associated with NHLs and analyzed the plasma cfDNA from patients with various subtypes using NGS; this study showed that the level of ctDNA was decreased in patients with response to therapy and increased in patients with disease progression [113]. However, we must be cautious because some reports have shown that some mutations, such as TP53 or DNMT3A, could have their origin in clonal hematopoiesis of indeterminate potential (CHIP) [99,114].…”

Mutation profiling of circulating tumor DNA identifies distinct mutation patterns in non‐Hodgkin lymphoma

“…Tissue biopsy is an invasive examination that can only reflect the characteristics of tumors statically and locally at the biopsy location. 28 Since ctDNA is derived from tumor cells throughout the body, it circumvents common limitations of tissue biopsies by capturing the complete molecular profile of tumors, including those from inaccessible anatomic locations. 27 In recent years, ctDNA emerges as an alternative source to estimate tumor burden and detect mutational profiles, 29 as well as represents a complementary method to PET scan imaging for DLBCL diagnosis.…”

Advances in Lymphoma Molecular Diagnostics

“…Liquid biopsy is a noninvasive procedure that allows for the detection of evidence of tumors in the peripheral blood [ 94 ]. In recent years, much scientific effort has been invested in the development of liquid biopsy, since it may overcome some of the difficulties related with the obtention of tissue probes for pathological analysis, such as difficult anatomical access, patients in critical condition, an unjustifiable risk of surgery, limited sensitivity of imaging technics for follow-up, amongst many others [ 95 , 96 ]. There are several methods of detecting tumor traces in the blood.…”

“…There are several methods of detecting tumor traces in the blood. Evidence of a malignancy may be present through the direct identification of circulating tumor cells, or indirectly through the investigation of genetic material released from tumor cells: DNA, microRNAs and tumor-derived exosomes [ 96 ]. DNA can be detected in the blood of virtually all individuals, and it is frequently named cell-free DNA (cfDNA).…”