The role of cell free DNA and liquid biopsies in haematological conditions

Abstract

Cell free nucleic acids (CFNAs) are nucleic acids released from cells that circulate within bodily fluids. Recent advances in molecular techniques have led to the ability to interrogate CFNAs in a clinically meaningful way, for example the identification and assessment of foetal CFNAs in maternal blood, allowing minimally invasive testing for foetal genetic abnormalities. The majority of CFNAs arise from haemopoietic cells, making it a particularly rich source of genetic information in haematological conditions. Furthermore, the innate genetic heterogeneity of haematological malignancies, as epitomised by multiple myeloma, lend itself well to "liquid biopsies". This approach promises to provide a more wholistic assessment of whole disease genetics, especially when contrasted against the current gold-standard of single site tissue biopsies. This review briefly summarises the definitions and physiology of CFNAs, both cell free DNA (cfDNA) and extracellular RNA (exRNA), before exploring the literature surrounding the current and future roles of cfDNA in the haematological malignancies and patient care.

Circulating cell‐free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre‐analytical biases

“…The emerging clinical benefits of ctDNA analysis in solid tumors have led over the last few years to an increasing interest also in hematologic malignancies, where many studies are now exploring its potential role for risk stratification, monitoring of tumor burden and response to treatment 12–17 . Given the unique characteristics of ctDNA, prior to a broad clinical implementation, several pre‐analytical factors must be addressed in order to achieve consistent and reproducible results.…”

“…10,11 The emerging clinical benefits of ctDNA analysis in solid tumors have led over the last few years to an increasing interest also in hematologic malignancies, where many studies are now exploring its potential role for risk stratification, monitoring of tumor burden and response to treatment. [12][13][14][15][16][17] Given the unique characteristics of ctDNA, prior to a broad clinical implementation, several pre-analytical factors must be addressed in order to achieve consistent and reproducible results. First, a rapid processing of samples is required after blood drawn before ctDNA is degraded by DNase or diluted by the lysis of normal leukocytes, which results in the release of large amounts of background genomic DNA (gDNA).…”