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 |
| . | 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 |