Correlation Analysis of DNA Methylation Level and Clinical Characteristics in JMML Patients

Objective: As a rare, aggressive pediatric myeloproliferative disease, juvenile myelomonocytic leukemia (JMML) encompassed both biological features of myelodysplastic syndrome and myeloproliferative neoplasm. Studies have shown that the methylation level in JMML patients is closely related to prognosis, and patients with high methylation level have poor prognosis. This study aimed to find clinical indicators that were associated with different methylation levels and prognosis.

Methods: The clinical information of 24 JMML patients with DNA samples admitted to our center from December 2013 to May 2020 was retrospectively analyzed, and the DNA methylation level of their whole genome was detected.

Results: The median age of onset was 14.5 months (0.1-153 months) among the 24 cases, including 17 males and 7 females. At diagnosis, the median WBC count was 27.1×10 ⁹/L (6.2-98.1×10 ⁹/L), and the median platelet count was 38×10 ⁹/L (10-277×10 ⁹/L). Chromosome karyotype abnormalities were found in 12.5% (3/24) of patients. Next-generation sequencing results showed that 79.2% (19/24) patients had at least one Ras pathway-related classical gene mutation, and 41.7% (10/24) patients had two or more somatic mutations. Genomic DNA methylation levels were divided into three groups: 10 cases in the hypomethylation group, 4 cases in the moderate methylation group, and 10 cases in the hypermethylation group. There were significant differences in age, platelets, PTPN11 gene mutation and the number of somatic mutations ≥2 in different methylation groups (P<0.05). The age of hypomethylated group was significantly lower than that of hypermethylated group (P<0.05), and the platelets of hypomethylated group was significantly higher than that of hypermethylated group (P<0.05). Patients ≤12m and platelets＞32×10 ⁹/L had lower DNA methylation level (P<0.0001). The number of patients with PTPN11 gene mutation in the hypomethylated group was significantly lower than that in the hypermethylated group (P<0.05), and the number of patients with ≥2 mutations in the low and medium methylated groups was significantly lower than that in the hypermethylated group (P<0.05). Correlation analysis showed that hypermethylation level was significantly correlated with PTPN11 gene mutation and ≥2 somatic mutations (P<0.001).

Conclusions: JMML patients with high methylation level in the DNA genome at diagnosis were older and with lower platelet levels, and hypermethylation were significantly correlated with high-risk prognostic factors such as PTPN11 gene mutation and ≥2 somatic mutations.

Figure 1

View largeDownload slide

Figure 1

View largeDownload slide

Close modal