Preferred Label : Juvenile myelomonocytic leukemia;
Symbol : JMML;
CISMeF acronym : JMML;
Type : Phenotype, molecular basis known;
Alternative titles and symbols : Leukemia, juvenile myelomonocytic;
Included titles and symbols : Leukemia, chronic myelomonocytic; CMML;
Description : Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome
(MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation
in the hematopoietic stem cell compartment with proliferation of differentiated progeny
(Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic
syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and
often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT),
some patients have been shown to have a prolonged and stable clinical course without
HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar
disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting
the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which
causes STAT5 (601511) hyperphosphorylation (Loh et al., 2009). - Genetic Heterogeneity
of Juvenile Myelomonocytic Leukemia In up to 60% of cases of JMML, the RAS/MAPK pathway
is deregulated due to somatic mutations in the PTPN11, KRAS, and NRAS genes. Additionally,
both germline and somatic mutations in the CBL gene have been found in patients with
JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009).
Somatic disruptions of the GRAF gene (ARHGAP26; 605370) have also been found in patients
with JMML. About 10 to 15% of JMML cases arise in children with neurofibromatosis
type I (NF1; 162200) due to germline mutations in the NF1 gene (613113). In addition,
patients with Noonan syndrome (NS1, 163950; NS3, 609942) or Noonan syndrome-like disorder
(NSLL; 613563) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively,
also have an increased risk of developing JMML. - Genetic Heterogeneity of Chronic
Myelomonocytic Leukemia Somatic mutations in the CBL, ASXL1 (612990), TET2 (612839),
and SF3B1 (605590) genes have been found in patients with CMML.;
Inheritance : Somatic mutation; Autosomal dominant;
Molecular basis : Caused by mutation in the CBL gene (CBL, 165360.0009); Caused by somatic mutation in the neuroblastoma Ras viral oncogene (NRAS, 164790.0003); Caused by somatic mutation in the Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene
homolog gene (KRAS, 190070.0003); Caused by somatic mutation in the RHO GTPase-activating protein 26 gene (ARHGAP26,
605370.0001); Caused by somatic mutation in the protein tyrosine phosphatase, nonreceptor-type,
11 gene (PTPN11, 176876.0014); Caused by mutation in the NF1 gene (NF1, 613113.0019);
Prefixed ID : #607785;
Origin ID : 607785;
UMLS CUI : C0349639;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- DO Cross reference
- Genes related to phenotype
- HPO term(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
- Validated automatic mappings to NTBT
