Levels of different DNA demethylation intermediates were associated with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) compared with controls from the general population, according to the results of a study published in the journal Cells.

There exists “major limitations in the current diagnostic approach to MDS/AML,” the authors wrote. The false-negative rates are estimated at 14% and 20% with bone marrow aspirates for AML and MDS, respectively, and discordance between diagnostic centers is as high as 12%.

“There is still space to introduce new diagnostic parameters,” they said. The aim of this study was to determine if DNA demethylation pathway intermediates have diagnostic and/or prognostic value, and if such markers can be used to identify higher risk for MDS transformation to AML.

Continue Reading

The study included newly-diagnosed, previously untreated patients with MDS (n=44) or AML (n=65) and a control cohort recruited from the general population (n=50). Basic cytometry was conducted of all patients to rule out any atypical cells in the peripheral blood. Levels of DNA demethylation intermediates were assessed from cells in peripheral blood or urine.

The presence of 5-(hydroxymethyl)-2’-deoxycytidine (5-hmdC) in the DNA from peripheral blood cells successfully identified patients with MDS from controls, with a sensitivity of 82% and a specificity of 98% (area under the curve [AUC], 0.905). The urinary excretion of 5-hydroxymethylcytosine (5-hmCyt) also discriminated patients with MDS from controls, with a sensitivity of 66% and a specificity of 92% (AUC, 0.746).

Patients with AML were successfully discriminated from controls by the urinary excretion of 5-hmCyt at a sensitivity and specificity of 85% and 97%, respectively (AUC, 0.918), and 5-(hydroxymethyl)-2’-deoxyuridine (5-hmdU) with a sensitivity and specificity of 74% and 92%, respectively (AUC, 0.873).

Patients with MDS and AML were classified correctly when using these intermediates and others as part of a multifactor model classification tree that uses supervised machine learning, with rates of 94.7% and 95.7%, respectively.

Transformation of MDS to AML was also predicted by the presence 5-hmdU with a sensitivity of 100% and specificity of 75% (AUC, 0.872) and 5-carboxy-2’-deoxycytidine with a sensitivity and specificity of 80% and 97%, respectively (AUC, 0.823), in the DNA from cells in peripheral blood.

The authors concluded that these data “can be useful in supporting the diagnostic process of patients with MDS and AML,” the authors wrote in their report. They added that there is also the “possibility of an early identification of a group of MDS patients with an increased risk of transformation into AML.”


Skalska-Bugala A, Starczak M, Szukalski L, et al. Diagnostic and prognostic power of active DNA demethylation pathway intermediates in acute myelogenous leukemia and myelodysplastic syndromes. Cells. 2022;11:888. doi: 10.3390/cells11050888