SERS-Based Assessment of MRD in Acute Promyelocytic Leukemia?

Abstract

Acute promyelocytic leukemia (APL) is characterized by a unique chromosome translocation t(15;17)(q24;q21), which leads to the PML/RARA gene fusion formation. However, it is acknowledged that this rearrangement alone is not able to induce the whole leukemic phenotype. In addition, epigenetic processes, such as DNA methylation, may play a crucial role in leukemia pathogenesis. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), involves the covalent transfer of a methyl group (-CH3) to the fifth carbon of the cytosine ring in the CpG dinucleotide and results in the formation of 5-methylcytosine (5-mC). The aberrant gene promoter methylation can be an alternative mechanism of tumor suppressor gene inactivation. Understanding cancer epigenetics and its pivotal role in oncogenesis, can offer us not only attractive targets for epigenetic treatment but can also provide powerful tools in monitoring the disease and estimating the prognosis. Several genes of interest, such as RARA, RARB, p15, p16, have been studied in APL and their methylation status was correlated with potential diagnostic and prognostic significance. In the present manuscript we comprehensively examine the current knowledge regarding DNA methylation in APL pathogenesis. We also discuss the perspectives of using the DNA methylation patterns as reliable biomarkers for measurable residual disease (MRD) monitoring and as a predictor of relapse. This work also highlights the possibility of detecting aberrant methylation profiles of circulating tumor DNA (ctDNA) through liquid biopsies, using the conventional methods, such as methylation-specific polymerase chain reaction (MS-PCR), sequencing methods, but also revolutionary methods, such as surface-enhanced Raman spectroscopy (SERS).

Recent advances in surface‑enhanced Raman spectroscopy based liquid biopsy for colorectal cancer (Review)

“…Recently, we have shown the correlation between DNA methylation pattern and SERS spectra, shedding light on a potential new method for cancer diagnosis (31,61). It is well known that cancer DNA has a tendency towards hypomethylation.…”

Advances in the application of Raman spectroscopy in haematological tumours

“…Abnormal methylation of gene promoters may be the inactivation mechanism of tumor suppressor genes. Studying cancer epigenetics and its key role in tumorigenesis through Raman spectroscopy can provide attractive epigenetic therapeutic targets and is a powerful tool for disease monitoring and prognosis estimation ( Turcas et al, 2020 ). The new Raman spectroscopy development technology compensates for the drawbacks of classic Raman scattering, such as excessive noise and poor signal intensity.…”

Editorial: Novel Drugs Targeting the Microenvironment and the Epigenetic Changes in Hematopoietic Malignancies

“…The concept of minimal residual disease (MRD) in oncological hematology is presented within this research topic ( Radu et al, 2020 ). In addition, DNA methylation patterns detected via revolutionary surface-enhanced Raman spectroscopy (SERS) are used as quantifiable biomarkers of circulating tumor cells in liquid biopsies ( Turcas et al, 2020 ).…”