title: [Juvenile myelomonocytic leukemias].
abstract: Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10(9)/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10(9)/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments.
authors.affiliation: CHU Robert-Debré, APHP, Département de génétique, 48, boulevard Sérurier, 75019 Paris, France, Inserm UMR1131, Institut universitaire d'hématologie, Université Paris-Diderot, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lachenaud
authors.affiliation: CHU Robert-Debré, APHP, Département de génétique, 48, boulevard Sérurier, 75019 Paris, France, Inserm UMR1131, Institut universitaire d'hématologie, Université Paris-Diderot, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Strullu
authors.affiliation: CHU Robert-Debré, APHP, Service d'immuno-hématologie pédiatrique, 48, boulevard Sérurier, 75019 Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: CHU Robert-Debré, APHP, Département de génétique, 48, boulevard Sérurier, 75019 Paris, France, Inserm UMR1131, Institut universitaire d'hématologie, Université Paris-Diderot, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
mesh_terms: D000293:Adolescent; D002648:Child; D015897:Comorbidity; D003937:Diagnosis, Differential; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D054429:Leukemia, Myelomonocytic, Juvenile / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D011379:Prognosis; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D035583:Rare Diseases / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D018631:ras Proteins / Q000378:metabolism
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D050721:Proto-Oncogene Proteins c-cbl; D018631:ras Proteins; C067419:CBL protein, human
keywords: Noonan syndrome; PTPN11; RAS; RAS pathway; juvenile myelomonocytic leukemia; monocytosis