-7/del(7q) in childhood

1999-06-01   François Desangles 

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 stem cell 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
  • Bibliography

    Pubmed IDLast YearTitleAuthors

    Summary

    Note

    -7/del(7q) is a more common entity of blood malignancies in the adults
    Atlas Image
    del(7q) G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen

    Citation

    François Desangles

    -7/del(7q) in childhood

    Atlas Genet Cytogenet Oncol Haematol. 1999-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/1152/7-del(7q)-in-childhood