Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Taking over the Atlas
Dear Colleagues,
The Atlas, once more, is in great danger, and I will have to proceed to a collective economic lay-off of all the team involved in the Atlas before the begining of April 2015 (a foundation having suddenly withdrawn its commitment to support the Atlas). I ask you herein if any Scientific Society (a Society of Cytogenetics, of Clinical Genetics, of Hematology, or a Cancer Society, or any other...), any University and/or Hospital, any Charity, or any database would be interested in taking over the Atlas, in whole or in part. If taking charge of the whole lot is too big, a consortium of various actors could be the solution (I am myself trying to find partners). Could you please spread the information, contact the relevant authorities, and find partners.
Survival of the Atlas will be critically dependant upon your ability to find solutions (and urgently!).
Kind regards.
Jean-Loup Huret
Donations are also welcome
If each casual visitor gives 3 Euros or Dollars, the Atlas is saved in a week !
If each professional gives 100 Euros or Dollars once a year (now), the Atlas is saved in 2 weeks !
Don't let the Atlas imminent demise
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Juvenile Chronic Myelogenous Leukemia (JCML)


ICD-Morpho 9946/3 Juvenile myelomonocytic leukemia
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

    Other genes implicated (Data extracted from papers in the Atlas)


    Translocations implicated (Data extracted from papers in the Atlas)


    Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells.
    Bollag G, Clapp DW, Shih S, Adler F, Zhang YY, Thompson P, Lange BJ, Freedman MH, McCormick F, Jacks T, Shannon K
    Nature genetics. 1996 ; 12 (2) : 144-148.
    PMID 8563751
    Juvenile chronic myelogenous leukemia.
    Hess JL, Zutter MM, Castleberry RP, Emanuel PD
    American journal of clinical pathology. 1996 ; 105 (2) : 238-248.
    PMID 8607451
    Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia.
    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.
    PMID 8971380
    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
    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
    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).
    Hasle H, Aricˆ¾ M, Basso G, Biondi A, Cantˆ¼ Rajnoldi A, Creutzig U, Fenu S, Fonatsch C, Haas OA, Harbott J, Kardos G, Kerndrup G, Mann G, Niemeyer CM, Ptoszkova H, Ritter J, Slater R, Starˆ‡ J, Stollmann-Gibbels B, Testi AM, van Wering ER, Zimmermann M
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 ; 13 (3) : 376-385.
    PMID 10086728
    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 and Gmcsf interact in myeloid leukemogenesis.
    Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, Jacks T, Clapp DW, Shannon KM
    Molecular cell. 2000 ; 5 (1) : 189-195.
    PMID 10678181
    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 (6) : 2310-2313.
    PMID 10979983
    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
    Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia.
    Bunin N, Saunders F, Leahey A, Doyle J, Calderwood S, Freedman MH.
    J Ped Hematol Oncol 1999; 21: 461-463.
    PMID 20065717
    Nf1 and GM-CSF interact in myeloid leukemogenesis.
    Birnbaum RA, O'Marcaigh A, Wardak Z, Zhang YY, Dranoff G, Jacks T, Clapp DW, Shannon KM.
    Molecular Cell 2000; 5: 189-195.
    PMID 20142671
    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 syndromes in children. A critical review of the clinical manifestations and mangement.
    Novitzky N.
    Am J Hematol 2000; 63: 212-222.
    PMID 20170720
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed


    Written12-2000Jay L. Hess


    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 ]
    URL :

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