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Juvenile Chronic Myelogenous Leukemia (JCML)

Written2000-12Jay L. Hess
Department of Pathology, The University of Michigan, M5240 Medical Science I, 1301 Catherine Avenue, Ann Arbor, MI 48109-0602, USA

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ICD-Morpho 9946/3 Juvenile myelomonocytic leukaemia
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1099
Note the proper terminology of this disorder is controversial; many authors, including the European Working Group on MDS in Childhood favor the term JMML; another working group suggests using the term JMML syndrome with a qualifier with or without monosomy 7 or 7q-
Other namesJuvenile myelomonocytic leukemia (JMML)
Juvenile myelomonocytic leukemia syndrome (JMML syndrome)

Clinics and Pathology

Disease JCML is a chronic myeloproliferative disorder that typically affects young children: more than 95% of cases are diagnosed before age 4
Phenotype / cell stem origin evidence exists for leukemic involvement of CD34-positive stem cells and monocyte-macrophage, erythroid, and B-lymphoid lineages in cases with cytogenetic abnormalities
Epidemiology annual incidence is estimated to be roughly 4/million; median age 1-4 yrs; sex ratio: 1.4M/1F
  • splenomegaly, lymphadenopathy, and skin rash are common; typical peripheral blood findings include leukocytosis (usually less than 100 x 109/L), monocytosis, and thrombocytosis with variable degree of left shift; myeloblasts average about 5% of total nucleated cells; elevation of fetal hemoglobin (hbF) very common; absence of the Philadelphia chromosome in all cases
  • proposed clinical criteria from the International Juvenile Myelomonocytic Leukemia Working Group includes: 1. white blood cell count > 13 x 109/L (corrected for nucleated red blood cells)
    2. absolute monocyte count > 1 x 109/L (corrected)
    3. presence of immature myeloid precursors (myelocytes, promyelocytes, and myeloblasts) in the peripheral blood
    4. bone marrow aspirate revealing < 30% blasts
    5. no Ph chromosome on cytogenetic assessment
  • about 15% of cases are associated with neurofibromatosis type 1 ( NF-1 mutation)
  • Pathology
  • blood: leukocytosis, monocytosis, left shift in myeloid maturation, circulating mucleated red blood cells
  • bone marrow: hypercellular marrow with mildly increased M:E ratio (typically 5:1), dispersed erythroid elements, and decreased numbers of megakaryocytes; dyplasia is usually not prominent
  • Treatment intensive chemotherapy and all trans retinoic have not been shown to induce durable remissions; complete remissions have been achieved with stem cell transplantation
    Prognosis the disease is uniformly fatal when treated with conventional chemotherapy; among those who undergo bone marrow transplantations, the majority ultimately relapse, with an overall survival rate of 25%


    Cytogenetics Morphological other than the frequent association with monosomy 7, no consistent cytogenetic abnormalities have been identified; whether the infantile monosomy 7 syndrome is distinct from JCML is controversial

    Genes involved and Proteins

    Note mechanisms of Oncogenesis:
    JCML patients show spontaneous growth of granulocyte-macrophage colony forming units (CFU-GM) from peripheral blood, which appears to be the result of hypersensitivity to GM-CSF, IL-3, or SCF; cases associated with NF-1 are likely to be the result of constitutive activation of the Ras pathway as a result of decreased GT Pase activity although there is also evidence of a GAP independent function; up to 30% of cases show mutations in K-ras and N-ras; the importance of the RAS pathway has been confirmed in mouse models with targeted disrupted of Nf-1; recently data suggest that TNFa produced by neoplastic cells may prevent expansion of hematopoietic progenitors


    Nf1 and GM-CSF interact in myeloid leukemogenesis.
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    Molecular Cell 2000; 5: 189-195.
    PMID 20142671
    Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells.
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    Nature genetics. 1996 ; 12 (2) : 144-148.
    PMID 8563751
    Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia.
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    J Ped Hematol Oncol 1999; 21: 461-463.
    PMID 20065717
    Evidence that juvenile myelomonocytic leukemia can arise from a pluripotential stem cell.
    Cooper LJ, Shannon KM, Loken MR, Weaver M, Stephens K, Sievers EL.
    Blood 2000; 96: 2310-2313.
    PMID 20435367
    Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS).
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    Juvenile chronic myelogenous leukemia.
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    American journal of clinical pathology. 1996 ; 105 (2) : 238-248.
    PMID 8607451
    Loss of heterozygosity of NF1 gene in juvenile chronic myelogenous leukemia with neurofibromatosis type 1.
    Kai S, Sumita H, Fujioka K, Takahashi H, Hanzawa N, Funabiki T, Ikuta K, Sasaki H
    International journal of hematology. 1998 ; 68 (1) : 53-60.
    PMID 9713168
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    Largaespada DA, Brannan CI, Jenkins NA, Copeland NG
    Nature genetics. 1996 ; 12 (2) : 137-143.
    PMID 8563750
    Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Children's Leukemia Cooperative Group (CLCG).
    Lutz P, Zix-Kieffer I, Souillet G, Bertrand Y, Dhooge C, Rubie C, Mazingue F, Marguerite F, Machinaud-Lacroix F, Rialland X, Plouvier E, Behar C, Vilmer E, Philippe N, Otten J
    Bone marrow transplantation. 1996 ; 18 (6) : 1111-1116.
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    Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management.
    Novitzky N
    American journal of hematology. 2000 ; 63 (4) : 212-222.
    PMID 10706766
    Myelodysplastic syndromes in children. A critical review of the clinical manifestations and mangement.
    Novitzky N.
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    PMID 20170720
    Juvenile myelomonocytic leukemia: what we don't know.
    Smith FO, Sanders JE
    Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 1999 ; 21 (6) : 461-463.
    PMID 10598653
    Nf1 regulates hematopoietic progenitor cell growth and ras signaling in response to multiple cytokines.
    Zhang YY, Vik TA, Ryder JW, Srour EF, Jacks T, Shannon K, Clapp DW
    The Journal of experimental medicine. 1998 ; 187 (11) : 1893-1902.
    PMID 9607929


    This paper should be referenced as such :
    Hess, JL
    Juvenile chronic myelogenous leukemia (JCML)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):35-36.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    External links

    COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9946/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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