Investigation of measurable residual disease in acute myeloid leukemia by DNA methylation patterns.

Assessment of measurable residual disease (MRD) upon treatment of acute myeloid leukemia (AML) remains challenging. It is usually addressed by highly sensitive PCR- or sequencing-based screening of specific mutations, or by multiparametric flow cytometry. However, not all patients have suitable mutations and heterogeneity of surface markers hampers standardization in clinical routine.

Chicken or Egg: Is Clonal Hematopoiesis Primarily Caused by Genetic or Epigenetic Aberrations?

Hematopoietic malignancies, including multiple myeloma, are associated with characteristic mutations and genetic instabilities that drive malignant transformation. On the other hand, tumor formation is also associated with drastic epigenetic aberrations, which can impact the genetic sequence. Therefore, the question arises if malignant transformation is primarily caused by genetic or epigenetic events.

Variants of cause transcript-specific DNA methylation patterns and affect hematopoiesis.

De novo DNA methyltransferase 3A (DNMT3A) plays pivotal roles in hematopoietic differentiation. In this study, we followed the hypothesis that alternative splicing of has characteristic epigenetic and functional sequels. Specific transcripts were either down-regulated or overexpressed in human hematopoietic stem and progenitor cells, and this resulted in complementary and transcript-specific DNA methylation and gene expression changes.

Leukocyte Counts Based on DNA Methylation at Individual Cytosines.

Background: White blood cell counts are routinely measured with automated hematology analyzers, by flow cytometry, or by manual counting. Here, we introduce an alternative approach based on DNA methylation (DNAm) at individual CG dinucleotides (CpGs).

Methods: We identified candidate CpGs that were nonmethylated in specific leukocyte subsets.

DNA-methylation in C1R is a prognostic biomarker for acute myeloid leukemia.

Background: Epigenetic aberrations play a central role in the pathophysiology of acute myeloid leukemia (AML). It has been shown that molecular signatures based on DNA-methylation (DNAm) patterns can be used for classification of the disease. In this study, we followed the hypothesis that DNAm at a single CpG site might support risk stratification in AML.