Liquid Biopsy in Hematologic Malignancies – Promise and Challenges

For most hematologic malignancies, the main diagnostic sample is from bone marrow biopsy or the use of imaging to detect lymphadenopathy. These procedures are either uncomfortable or maybe associated with radiation and may lack sensitivity. Some of the hematologic malignancies such as multiple myeloma may have patchy involvement, and also spatial heterogeneity, as such a single biopsy may not adequately represent disease biology. These issues could potentially be overcome by liquid biopsies which allow disease detection, biological assessment and disease monitoring using the ease of a blood sample. The range of information that can be obtained has also increased significant to now include, circulating tumor cells, cell free DNA (mutations of genes or aneuploidy), miRNA, and DNA methylation. Microfluidics devices has been developed to quantitate circulating tumor cells. Some of these devices are based on physical properties rather than protein makers and may allow the recovery of live cells for further studies. In addition, the ability to harvest circulating tumor cells also allow the study of drug resistant residual cells, so that these may be specific targeted. The use of blood allows regular monitoring as opposed to regular scans or bone marrow examination which is not feasible. While liquid biopsy holds much promise, there are several areas that are unresolved. For one, which type of information will be most useful? Is the sensitivity good enough for minimal residual disease monitoring? Can it replace current diagnostic, prognostic or monitoring test? Liquid biopsy is an important advance even for haematologic malignancies but there are some issues that requires further resolution. Ongoing studies will provide further insights in the coming years.