The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response

Różalski, Rafał; Gackowski, Daniel; Skalska-Bugała, Aleksandra; Starczak, Marta; Siomek-Górecka, Agnieszka; Zarakowska, Ewelina; Modrzejewska, Martyna; Dziaman, Tomasz; Szpila, Anna; Linowiecka, Kinga; Guz, Jolanta; Szpotan, Justyna; Gawroński, Maciej; Labejszo, Anna; Gackowska, Lidia; Foksiński, Marek; Olinska, Elwira; Wasilow, Aleksandra; Kołtan, Andrzej; Styczyński, Jan; Oliński, Ryszard

doi:10.1038/s41598-021-00880-9

Cited by 5 publications

(1 citation statement)

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“…The chromatographic system was operated in heart-cutting mode, which means that selected portions of effluent from the first dimension were loaded onto the trap/transfer column by a 6-port switching valve, which served as an “injector” for the second dimension of the chromatography system. Mass spectrometric detection was conducted with a Waters Xevo TQ-S tandem quadrupole mass spectrometer equipped with a UniSpray ionization source as previously described by Rozalski et al [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Skalska-Bugała

Starczak

Szukalski

et al. 2022

Cells

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Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by genomic instability, which may arise from the global hypomethylation of the DNA. The active DNA demethylation process may be linked with aberrant methylation and can be involved in leukemogenesis. The levels of 5-methylcytosine oxidation products were analyzed in minimally invasive material: the cellular DNA from peripheral blood cells and urine of patients with AML and MDS along with the control group, using isotope-dilution two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. The receiver operating characteristic curve analysis was used for the assessment of the ability to discriminate patients’ groups from the control group, and AML from MDS. The most diagnostically useful for discriminating AML patients from the control group was the urinary excretion of 5-hydroxymethylcytosine (AUC = 0.918, sensitivity: 85%, and specificity: 97%), and 5-(hydroxymethyl)-2′-deoxyuridine (0.873, 74%, and 92%), while for MDS patients 5-(hydroxymethyl)-2′-deoxycytidine in DNA (0.905, 82%, and 98%) and urinary 5-hydroxymethylcytosine (0.746, 66%, and 92%). Multi-factor models of classification trees allowed the correct classification of patients with AML and MDS in 95.7% and 94.7% of cases. The highest prognostic value of the analyzed parameters in predicting the transformation of MDS into AML was observed for 5-carboxy-2′-deoxycytidine (0.823, 80%, and 97%) and 5-(hydroxymethyl)-2′-deoxyuridine (0.872, 100%, and 75%) in DNA. The presented research proves that the intermediates of the active DNA demethylation pathway determined in the completely non-invasive (urine) or minimally invasive (blood) material can be useful in supporting the diagnostic process of patients with MDS and AML. The possibility of an early identification of a group of MDS patients with an increased risk of transformation into AML is of particular importance.

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Section: Methodsmentioning

confidence: 99%