[Objective] Juvenile myelomonocytic leukemia (JMML) is a rare abnormal clonal disease of hematopoietic stem cells in infants. Epigenetic abnormality is a prominent feature of JMML. DNA methylation is an important component of epigenetics. The level of abnormal methylation level in patients with JMML is closely related to prognosis. The latest international consensus on JMML methylation monitoring pointed out that the characteristics of JMML genome and epigenome provide an important means for the study of prognostic stratification and pathogenesis of JMML. However, there is a lack of understanding of clinical characteristics among patients with different levels of JMML methylation. This study retrospectively analyzed the initial methylation level of JMML in a single center and conducted risk stratification to explore the correlation between JMML methylation level and clinical characteristics.

[Methods] The clinical information of patients with JMML and methylation data in our center was collected. Patients were divided into 2 groups by JMML methylation consensus standard. The laboratory examination results of clinical characteristics of different methylation levels of JMML were summarized, and the relationship between methylation level and clinical prognosis was analyzed.

[Results] A total of 29 patients were enrolled in this study from 2015.6 to 2022.7. The median age of onset was 28 (range 3-60) months. There were 21 males (male: female = 2.6). According to the consensus criteria of methylation, JMML methylation levels were divided into two groups: hypomethylation group (LM) (n = 14) and hypermethylation group (HM) (n = 15). The median age of onset in LM group was 16.7(range 3.0-47.0) months, which was lower than that in HM group38.6 (range 3 to 60 months). The median interval from onset to diagnosis was 5.2 (range 0.2-18.0) months vs 3.7 (range 0.1-24.0) months (F= 0.121,P=0.730). The median platelet count of 71.3 (range 13.0-259.0) × 109 vs L (range 10.0-74.0) × 109 LIM group was significantly higher than that of HM group (P < 0.05). The median HbF 10.3 (range 1.4-49.5)% vs 43.0 (range 1.7-76.1)% (Fang 2.991), HbF in HM group. It was significantly higher than that in the LIM group, and the trend of increase was not statistically significant because of the small number of cases. All the 15 patients in the HM group carried JMML classical gene mutations, including 13 cases carrying PTPN11 somatic mutations (86.7%), the other 2 cases carrying NRAS mutations and 8 cases carrying more than two classical mutations (53.3%), including 4 cases of PTPN11/NF1 mutations, 3 cases of PTPN11/NRAS mutations and 1 case of NRAS/KRAS. In LIM group, 10 cases (71.4%) carried classical mutations, including 3 cases of PTPN11 mutations, 2 cases of NF1 -, 3 cases of NRAS and 2 cases of KRAS. No cases with more than two classical gene mutations were detected. The secondary mutation HM group mainly included 3 cases of SETBP1 (20%), 3 cases of JAK3 (20%), 2 cases of ARID1A and FAT1 (13.3%), 3 cases of TET2-3 (21.4%) and 1 case of RANBP2-ALK fusion (7.1%) in LIM group.

[Conclusion] JMML is a rare myelodysplastic syndrome / myeloproliferative tumor (MDS/MPN) in infants. Recent studies have found that the level of methylation is closely related to the prognosis of JMML. The results of this study showed that the median age of onset of HM was higher, the number of newly diagnosed platelets was significantly lower, and the proportion of PTPN11 with poor prognosis was higher. The incidence of more than two gene mutations was as high as 53.3%, and secondary mutations such as SETBP1 and JAK3 were more common in HM group. The clinical characteristics of HM group are closely related to the currently recognized adverse risk factors of JMML. Due to the small number of cases, the prognosis of different methylation levels and the correlation with treatment and intervention still need to be further studied.

No relevant conflicts of interest to declare.

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Asterisk with author names denotes non-ASH members.

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