-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

    • Article Bibliography

    Pubmed IDLast YearTitleAuthors
    1038071419995th International Symposium on Myelodysplastic Syndromes. Prague, Czech Republic, 21-24 April 1999. Abstracts.
    22976851990Monosomy 7 syndrome. Clinical heterogeneity in children and adolescents.Daghistani D et al
    90587251997Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias.Fischer K et al
    103748511999Neutrophil dysplasia is not a specific feature of the abnormal chromosomal clone in myelodysplastic syndromes.Hast R et al
    86116801996Molecular definition of a narrow interval at 7q22.1 associated with myelodysplasia.Johnson EJ et al
    100710861999Allelotyping of acute myelogenous leukemia: loss of heterozygosity at 7q31.1 (D7S486) and q33-34 (D7S498, D7S505).Koike M et al
    88229091996Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases.Le Beau MM et al
    95204441998Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: evidence for multiple critical loci.Liang H et al
    77188701995Childhood monosomy 7: epidemiology, biology, and mechanistic implications.Luna-Fineman S et al
    75645191995Glutathione-S-transferases pi, alpha, mu and mdr1 mRNA expression in normal lymphocytes and chronic lymphocytic leukemia.Marie JP et al
    97310471998Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation.Nevill TJ et al
    77034821995Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system.Passmore SJ et al
    19543851991Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy.Rubin CM et al
    86372181996Deletion of the acetylcholinesterase locus at 7q22 associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML).Stephenson J et al

    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