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Article

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

1
Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland
2
Department of Hematology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-168 Bydgoszcz, Poland
3
Department of Human Biology, Institute of Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland
4
Department of Geriatrics, Division of Biochemistry and Biogerontology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland
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Clinic of Hematology, University Hospital No. 2—Jan Biziel Memorial Hospital, 85-168 Bydgoszcz, Poland
6
Department of Hematology, Nicolaus Copernicus Hospital, 87-100 Toruń, Poland
*
Authors to whom correspondence should be addressed.
Those authors equally contributed to the work.
Academic Editor: Alexander E. Kalyuzhny
Cells 2022, 11(5), 888; https://doi.org/10.3390/cells11050888
Received: 25 January 2022 / Revised: 22 February 2022 / Accepted: 2 March 2022 / Published: 4 March 2022
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. View Full-Text
Keywords: acute myelogenous leukemia; myelodysplastic syndromes; biomarkers; active demethylation; 5-hydroxymethylcytosine; 5-carboxycytosine; 5-formylcytosine; 5-hydroxymethyluracil; ROC; classification trees acute myelogenous leukemia; myelodysplastic syndromes; biomarkers; active demethylation; 5-hydroxymethylcytosine; 5-carboxycytosine; 5-formylcytosine; 5-hydroxymethyluracil; ROC; classification trees
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MDPI and ACS Style

Skalska-Bugala, A.; Starczak, M.; Szukalski, Ł.; Gawronski, M.; Siomek-Gorecka, A.; Szpotan, J.; Labejszo, A.; Zarakowska, E.; Szpila, A.; Jachalska, A.; Szukalska, A.; Kruszewski, M.; Sadowska, A.; Wasilow, A.; Baginska, P.; Czyz, J.; Olinski, R.; Rozalski, R.; Gackowski, D. Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes. Cells 2022, 11, 888. https://doi.org/10.3390/cells11050888

AMA Style

Skalska-Bugala A, Starczak M, Szukalski Ł, Gawronski M, Siomek-Gorecka A, Szpotan J, Labejszo A, Zarakowska E, Szpila A, Jachalska A, Szukalska A, Kruszewski M, Sadowska A, Wasilow A, Baginska P, Czyz J, Olinski R, Rozalski R, Gackowski D. Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes. Cells. 2022; 11(5):888. https://doi.org/10.3390/cells11050888

Chicago/Turabian Style

Skalska-Bugala, Aleksandra, Marta Starczak, Łukasz Szukalski, Maciej Gawronski, Agnieszka Siomek-Gorecka, Justyna Szpotan, Anna Labejszo, Ewelina Zarakowska, Anna Szpila, Anna Jachalska, Adriana Szukalska, Marcin Kruszewski, Anna Sadowska, Aleksandra Wasilow, Patrycja Baginska, Jaroslaw Czyz, Ryszard Olinski, Rafal Rozalski, and Daniel Gackowski. 2022. "Diagnostic and Prognostic Power of Active DNA Demethylation Pathway Intermediates in Acute Myelogenous Leukemia and Myelodysplastic Syndromes" Cells 11, no. 5: 888. https://doi.org/10.3390/cells11050888

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