TABLE 2.

Overview of various studies demonstrating the utility of ctDNA for molecular characterization, disease monitoring, and clinical outcome in acute myeloid leukemia.

Study focus	Patients/controls	Molecular method	Gene target	Major findings	Clinical significance	References
Point mutation	10	Southern hybridization/allele-specific PCR	N-RAS	Plasma is easily accessible and useful for detection and monitoring of myeloid disorders	Diagnostic Prognostic	Vasioukhin et al. (1994)
LOH	45/30	Multiplex PCR of microsatellite markers, sequencer	5q, 7q, 8, 17p, 20q	PB plasma is enriched in ctDNA; carry genomic aberrations	Diagnostic	Rogers et al. (2004)
DNA concentration	25	Spectrophotometry	–	Nucleosomal DNA is valuable marker for early prediction of therapeutic efficacy.	Diagnostic Prognostic therapy response	Mueller et al. (2006)
DNA concentration and integrity	60/30	qPCR	ACTB	Plasma DNA integrity is increased in acute leukemia and useful for monitoring MRD	Prognostic	Gao et al. (2010)
DNA concentration	66/100	Duplex real-time qPCR		Quantification of plasma DNA is useful for evaluating therapeutic effects and monitoring relapse	Diagnostic Prognostic	Jiang et al. (2012)
Mutation	100	qRT-PCR	NPM1	Circulating NPM mutations DNA assay serves as a complementary to routine investigative protocol	Diagnostic	Quan et al. (2015)
Gene rearrangement	235	qPCR	IGH or TCR gene rearrangement	Monoclonal IGH and TCR rearrangement in cfDNA may represent a useful tool for MRD monitoring	Prognostic	Zhong et al. (2018)
Mutations	53	NGS, ddPCR	57 targets	ctDNA predicts relapse post-alloSCT in AML and MDS	Diagnostic Prognostic	Nakamura et al. (2019)
Mutations	22	Targeted NGS	28 targets	cfDNA and bone marrow may be complementary in the assessment and monitoring of patients with AML.	Diagnostic Prognostic	Short et al. (2020)