Project description:Assessment of measurable residual disease (MRD) upon treatment of acute myeloid leukemia (AML) remains a challenge. It is usually addressed by highly sensitive PCR-based screening of disease-specific mutations or multiparametric flow cytometry. However, not all patients have suitable mutations to track the disease and heterogeneity of applied surface markers hampers standardization in clinical routine. In this study, we propose an alternative approach to estimate MRD based on AML-associated DNA methylation (DNAm) patterns. We identified four CG dinucleotides (CpGs) that commonly reveal aberrant DNAm in AML and their combination could reliably discern healthy and AML samples. Interestingly, many of these aberrations are shown to affect both alleles. Using bisulfite amplicon sequencing (BA-seq), we captured local DNAm patterns flanking these AML associated CpGs, and trained shallow-learning and deep-learning algorithms to identify anomalous, non healthy DNAm patterns within the amplicons. The method was then tested on follow-up samples with and without MRD status. Notably, many MRD negative samples revealed higher anomaly ratios than healthy controls. Our results demonstrate that targeted DNAm analysis facilitates reliable discrimination of malignant and healthy samples. However, even after successful treatment aberrant DNAm patterns persist in some samples that were classified as MRD negative.

2021-06-16 | GSE166264 | GEO

Phenotypic and genotypic characteristics of MSSA isolates responsible for infective endocarditis

Project description:Phenotypic and genotypic characteristics of MSSA isolates responsible for infective endocarditis

| PRJEB82234 | ENA

Cell-free DNA 5-hydroxymethylcytosine is highly sensitive for MRD assessment in acute myeloid leukemia

Project description:Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). However, MRD cannot be detected in many patients using current methods. We developed a highly sensitive 5-hydroxymethylcytosine (5hmC) signature in cell-free DNA by analyzing 115 AML patients and 86 controls. The 5hmC method detected MRD in 20 of 29 patients with negative MRD by multiparameter flow cytometry and 11 of 14 patients with negative MRD by molecular methods. MRD detection by the 5hmC method was significantly associated with relapse-free survival. This novel method can be used in most AML patients and may significantly impact AML patient management.

2023-12-31 | GSE237057 | GEO

Autonomous TGFβ signaling induces phenotypic variation in human acute myeloid leukemia

Project description:Autonomous TGFβ signaling induces phenotypic variation in human acute myeloid leukemia

| PRJNA631038 | ENA

Project description:FLT3-TKD measurable residual disease in acute myeloid leukemia

| PRJNA979814 | ENA