Liquid biopsy in hematological malignancies: current and future applications

Abstract

The assessment of the cancer mutational profile is crucial for patient management, stratification, and therapeutic decisions. At present, in hematological malignancies with a solid mass, such as lymphomas, tumor genomic profiling is generally performed on the tissue biopsy, but the tumor may harbor genetic lesions that are unique to other anatomical compartments. The analysis of circulating tumor DNA (ctDNA) on the liquid biopsy is an emerging approach that allows genotyping and monitoring of the disease during therapy and follow-up. This review presents the different methods for ctDNA analysis and describes the application of liquid biopsy in different hematological malignancies. In diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), ctDNA analysis on the liquid biopsy recapitulates the mutational profile of the tissue biopsy and can identify mutations otherwise absent on the tissue biopsy. In addition, changes in the ctDNA amount after one or two courses of chemotherapy significantly predict patient outcomes. ctDNA analysis has also been tested in myeloid neoplasms with promising results. In addition to mutational analysis, liquid biopsy also carries potential future applications of ctDNA, including the analysis of ctDNA fragmentation and epigenetic patterns. On these grounds, several clinical trials aiming at incorporating ctDNA analysis for treatment tailoring are currently ongoing in hematological malignancies.

Keywords: DLBCL; Hodgkin lymphoma; liquid biopsy; myeloid neoplasia; precision medicine.

Figure 1

Liquid biopsy as a tool for identifying various cancer-specific analytes. Tumor-specific circulating analytes potentially detected by liquid biopsy include cell-free DNA (cfDNA) and/or circulating tumor DNA (ctDNA), circulating cells (CTCs), extracellular vesicles (EVs), and tumor-educated platelets (TEPs). Different cancer-specific genomic signatures can be revealed from ctDNA, including mutations, copy number alterations (CNAs), fragmentomics, and DNA methylation patterns. These biological data could be integrated using innovative bioinformatic pipelines to improve precision medicine.

Figure 2

ctDNA collection method and analysis. (A) describes ctDNA isolation and extraction from peripheral blood (PB); (B) summarizes the main ctDNA applications in hematological malignancies.