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-7/del(7q) in childhood

Written1999-06François Desangles
Laboratoire de Biologie, Hopital du Val de Grace, 75230 Paris, France

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1152
Note -7/del(7q) is a more common entity of blood malignancies in the adults
 
  del(7q) G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen

Clinics and Pathology

Disease myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML); may occur:

1- de novo,
2- be secondary to treatments with alkylating agents, or
3- in patients with predisposing leukemia syndromes: Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, Neurofibromatosis type I,Down syndrome, familial monosomy 7;

Phenotype / cell stem origin MDS cases : more often RAEB/RAEB-T, CMML, or the following specific childhood presentations : juvenile chronic leukemia (JCML), and monosomy 7 syndrome; AML most often M4 or M6
Epidemiology the most frequent abnormality in childhood myeloid disorders; found in 30% of the MDS and in 4% of the AML; sex/age: 90% of the children with this anomaly are younger than 5 years; before 5 years, there is a majority of boys (3M/2F), with -7 as the sole cytogenetic abnormality; after 5 years, girls are in majority, and the -7/del(7q) is then often associated with additional anomalies
Clinics several clinical forms: the most frequents are JCML and the monosomy 7 syndrome; these disorders have some common features:
  • JCML is defined by clinical and cytological observations; 6 to 24% of JCML
  • children show monosomy 7 in the bone marrow;
  • monosomy 7 syndrome is a cytogenetic-defined entity
  • the therapy related cases of monosomy 7 had been exposed to alkylating agents, they have a myelodysplastic phase preceding acute leukemia with multilineage bone marrow dysplasia. In opposite, therapy including anti-topoisomerase drug induce myelodysplastic syndromes and leukemias with 11q23 abnormalities
    • Cytology
  • before 5 years, the disease presents as a specific myeloid leukemia characterized by leucocytosis with monocytosis but thrombopenia, anemia in blood and hyperplasia of the bone marrow; for some authors, the diagnosis of monosomy 7 syndrome should be made in any FAB class (principally CMML), whereas the diagnosis of JCML applies to cases of CMML with fetal hemoglobin > 10 %,and with no monosomy 7; the remaining CMML are diagnosed as CMML; for others, a - 7 does not exclude the diagnosis of JCML; however, cases of JCML without visible monosomy 7 appear to have no loss of heterozygosity on chromosome 7
  • after 5 years, the disease presents as a MDS with cytopenia in blood and hypodysplasia of bone marrow, like in adults
    • Prognosis slow evolution of the AML in infants before 6 month; for children older than 1 year, the survival is less than 2 years; the European Working Group on MDS in Childhood noted a superior survival for children with MDS having a - 7 alone than for those with other anomalies (3 yr survival of 56% vs 24% ); but this was the reverse in children with AML

    Cytogenetics

    Cytogenetics Morphological deletion (7q): cluster of breakpoints in 7q11 to 7q36, is a with two common minimal zones in q22 and in q32-34
    Cytogenetics Molecular using loss of heterogygocity (LOH) studies and YAC libraries, a 2 to 3 Mb segment in 7q22 has been designated as the proximal common deleted area; the 7q33-34 zone is the consensual area for the distal deletion; LOH studies suggest that a specific mechanism, such as mitotic recombination in bone marrow stem cell leading to homozygosity in both granulocytes and lymphocytes, may be implicated
    Additional anomalies
  • 7 alone is observed in 75% of MDS cases and in 32% of AML; the specific additional anomalies are -5/del(5q), and trisomy 8
    • Variants the balanced translocation t(1;7)(q10;p10), and many unbalanced translocation, having for consequence a partial monosomy 7 of the 7q22 to 7q34 bands may, in a way, be considered as variants

    Genes involved and Proteins

    Note -7/del(7q) is frequent in secondary MDS or AML, and also in leukemias occurring in individuals with constitutional syndromes including predisposition to myeloid disorders; these findings suggest the presence of a putative myeloid leukemia suppressor gene in the commonly deleted genomic segment 7q22 and even multiple genes in 7q22 -31.1 that are playing a role in leukemogenesis;

    candidate genes are :

  • ASNS (asparagine synthetase gene) in 7q21.3-q22.1;
  • ACHE (acetyl cholinesterase),
  • EPO (erythropoietin),
  • PLANH1 (plasminogen activator inhibitor 1) in 7q22; and
  • MET in 7q31.2-31.3
    •

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    Citation

    This paper should be referenced as such :
    Desangles, F
    -7/del(7q) in childhood
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):141-143.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/del7qChildID1152.html

    External links

    arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMapTopo ( C42) Morph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
     
    Disease database-7/del(7q) in childhood
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