Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma

Abstract

Liquid biopsy is one of the fastest emerging fields in cancer evaluation. Circulating tumour cells and tumour-originated DNA in plasma have become the new targets for their possible employ in tumour diagnosis, and liquid biopsy can define tumour burden without invasive procedures. Multiple Myeloma, one of the most frequent hematologic tumors, has been the target of therapeutic progresses in the last few years. Bone marrow aspirate is the traditional tool for diagnosis, prognosis, and genetic evaluation in multiple myeloma patients. However, this painful procedure presents a relevant drawback for regular disease examination as it requires an invasive practice. Moreover, new data demonstrated that a sole bone marrow aspirate is incapable of expressing the multifaceted multiple myeloma genetic heterogeneity. In this review, we report the emerging usefulness of the assessment of circulating tumour cells, cell-free DNA, extracellular RNA, cell-free proteins, extracellular vesicles, and tumour-educated platelets to evaluate the changing mutational profile of multiple myeloma, as early markers of disease, reliable predictors of prognosis, and as useful tools to perform less invasive monitoring in multiple myeloma.

Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenström macroglobulinemia during treatment with BTK inhibitors

“…Liquid biopsy is increasingly utilized in treatment of hematologic malignancies and has made great contributions. Many studies have illustrated the potential of liquid biopsy approaches for diagnosis, therapy, assessment of MRD, early detection of relapse and prognosis in aggressive B-cell lymphomas, acute myeloid leukemia, myelodysplastic syndrome, chronic lymphocytic leukemia and multiple myeloma ( 12 – 15 ). This cost-efficient method can prevent the discomfort and complexity caused by repeated bone marrow biopsy in WM.…”

Minimal Residual Disease in Multiple Myeloma: Past, Present, and Future

“…Overall, liquid biopsies may provide a dynamic and comprehensive picture of the genomic landscape in MM and, even more, a non-invasive approach to monitor tumor burden. However, these methods are still novel and demand further research, especially when comparing results with matched BM assessments [137,138]. Therefore, the implementation of liquid biopsies for MM requires validation and harmonization of the assays [123].…”

Label-Free Enrichment of Circulating Tumor Plasma Cells: Future Potential Applications of Dielectrophoresis in Multiple Myeloma

“…Indeed, differently from neoplastic PCs in the bone marrow, CTPCs in MM are mostly apoptopic (arrested in the G0–G1 phase of the cell cycle) [ 14 ], with a significantly lower proliferation index than their BM counterpart, following a circadian rhythm similar to CD34+ cells [ 15 ]. Thus, CTPCs are highly informative about both intra and extramedullary disease at the phenotypic, genomic and transcriptomic levels [ 16 ].…”

“…Using ultra-low pass whole-genome sequencing (ULP-WGS), CTPCs can capture the genetic diversity of matched tumor biopsies, leading to identification of subclones not detectable in the bone marrow. However, the major limitation to the genomic evaluations for CTPCs was the enrichment step, which could result in substantial carryover of white blood cells and affect the ability to detect limited numbers of CTPCs [ 16 ].…”