Correlation Analysis of DNA Methylation Level and Clinical Characteristics in Pediatric MDS Patients

Objective: Pediatric myelodysplastic syndrome (MDS) has a considerably lower prevalence compared to MDS in adults, with an annual incidence rate ranging from 1 to 2 cases per million children.This study aimed to find clinical indicators that were associated with different methylation levels and prognosis.

Methods: The clinical data of 20 pediatric MDS patients with DNA samples admitted to our center from April 2017 to December 2020 were retrospectively analyzed, Quantification of DNA methylation was performed using an Illumina Infinium MethylationEPIC Beadchip platform (Illumina). Unsupervised hierarchical clustering of the most variable CpG sites across all MDS samples classified three clusters, low methylation (LM), intermediate methylation (IM), and high methylation (HM).

Results: 20 cases of pediatric MDS were admitted to our study，according to WHO 2016 myeloid tumor diagnosis criteria RCC 7 RAEB 10 and RAEB-T 3cases. The median age of onset was 7.9 years old (3.5-14.9 years) among the 20 cases, including 13 males and 7 females. At diagnosis, the median WBC count was 13.0×10⁹/L (1.4-130.0×10⁹/L), the median platelet count was 81.1×10⁹/L (18.0-254.0×10⁹/L) the median MCV was 95.5fl (79.2-124.1fl) and the median RDW-SD 56.7fl (13.7-109.6), RDW-CV 19.6 (13.7-57.2). Chromosome karyotype abnormalities were found in 80% (16/20) of patients, 9 cases(56.3%) had chromosome 7 deletion. Genomic DNA methylation levels were classified into three groups: 2 cases in the LM subgroup,9 cases IM subgroup, and 9 cases in the HM subgroup. 16 cases were given hemotopoietic stem cell transplantation(HSCT), There were significant differences in counts of white blood cell(WBC), neutrophil and platelets in different methylation subgroups (P<0.05). All patients were followed up to July 2024, 2 cases lost follow-up. The median overall survival(OS) was 63.6%±11%, the median event free survival(EFS）was 64.6%±18.8%. There were no differnce in OS and EFS among different methylation groups. Compared with the LM and IM subgroup, the HM group had higher WBC (5.17 vs 2.5, 0.01) and neutrophil absolute value (3.03 vs 0.52,0.025), and lower platelet (47 vs 76, 0.067).

Conclusions: Pediatric MDS patients with HM at diagnosis had higher WBC counts and neutrophil, and with lower platelets. In our study There was no significant difference in survival among different methylation groups.

No relevant conflicts of interest to declare.