HAEM5:Juvenile myelomonocytic leukaemia: Difference between revisions

Children with JMML typically present with symptoms related to infiltration of the bone marrow and other organs. Approximately one half of all patients have lymphadenopathy (WHO), and one-third of children will have an acute presentation with fever, signs of upper respiratory infection, organomegaly, and cutaneous findings (Caywood and Kolb, UpToDate).  

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==Sites of Involvement==

Chromosomal translocations resulting in fusion genes have been only rarely reported in JMML patients with monosomy 7 (without mutations in the canonical RAS pathway)<ref>{{Cite journal|last=Meynier|first=Sonia|last2=Rieux-Laucat|first2=Frédéric|date=2020-09|title=After 95 years, it's time to eRASe JMML|url=https://pubmed.ncbi.nlm.nih.gov/31980238|journal=Blood Reviews|volume=43|pages=100652|doi=10.1016/j.blre.2020.100652|issn=1532-1681|pmid=31980238}}</ref>.

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

The progression of JMML is variable. While some studies identify a prognostic difference based on the molecular driver mutation, with ''PTPN11, KRAS,'' and ''NRAS'' mutations showing a more aggressive disease course (WHO: Baumann I et al), another report identified the number of mutations present at diagnosis (rather than the type of mutations), as a prognostic factor, with patients harboring two or more somatic alterations at diagnosis having worst event-free and overall survival rates than those with one or no mutations (Stieglitz E et al, <nowiki>PMID 26457647</nowiki>). Spontaneous regression of JMML is observed in most children with ''CBL'' mutations. The only curative treatment is allogeneic stem cell transplant, with a 5-year event free survival of approximately 44-53% (Meynier S and  Rieux-Laucat, <nowiki>PMID 31980238</nowiki>).

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==Individual Region Genomic Gain / Loss / LOH==

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|'''Prevalence'''

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==Gene Mutations (SNV / INDEL)==

Frequent gene mutations<ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|date=2018-11-30|title=JMML genomics and decisions|url=https://pubmed.ncbi.nlm.nih.gov/30504325|journal=Hematology. American Society of Hematology. Education Program|volume=2018|issue=1|pages=307–312|doi=10.1182/asheducation-2018.1.307|issn=1520-4383|pmc=6245977|pmid=30504325}}</ref> are summarized below:

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==Epigenomic Alterations==

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Molecular driver mutations within the RAS signaling pathway genes ''PTPN11'', ''NRAS'', ''KRAS'', ''NF1'', and ''CBL'' are identified in 85-90% of patients with JMML.  

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==Genetic Diagnostic Testing Methods==

==Familial Forms==