Table 2.

Genetic, epigenetic, and clinical characteristic of genetic JMML subtypes

	PTPN11	KRAS	NRAS	NF1	CBL
Prevalence	∼35-40%	∼15%	∼15-20%	∼10-15%	∼10-15%
Configuration	Germline or somatic	Germline or somatic	Germline or somatic	Germline + LOH	Germline ± LOH or somatic ± LOH
Genetic characteristics	Frequent co-occurence with secondary mutations including in NF1	Frequent association with monosomy 7	Can co-occur with SETBP1 mutations	Two-thirds of cases have LOH via uniparental disomy	Secondary mutations in additional genes are exceedingly rare
Most common DNA methylation subgroup(s)	High	Intermediate	Low	Intermediate or high	Low
Germline characteristics	Can present with MPD of infancy	Can present with MPD of infancy	Can present with MPD of infancy	Older age at disease onset Higher platelet count Fatal without HCT High probability of treatment-related mortality	Possibility of spontaneous resolution Indication for HCT is unclear
Somatic characteristics	Older age at diagnosis Rapidly fatal without HCT High incidence of relapse after HCT	Heterogenous outcomes	Typically occurs in infants and toddlers Heterogenous outcomes	Somatic-only NF1 mutations are rare but possible	Somatic-only CBL mutations can be associated with a more aggressive disease course