-7/del(7q) in adults

1999-06-01   François Desangles 

Clinics and Pathology

Disease

myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML); they may occur de novo, or be secondary to an exposure to chemical mutagens or to chemotherapy treatments with alkylating agents; may probably also be secondary to immunosuppressive therapy for severe aplastic anemia

Phenotype stem cell origin

  • MDS cases : found in 30% of RAEB/RAEB-T, 20% of CMML, and only 5% of RA with an abnormal karyotype;
  • AML most often M4 or M6 ;
  • Monosomy 7 and these deletions does not seem a specific feature of the dysplastic clone in the MDS, they are secondary events contributing to the leucogenesis

    • Epidemiology

    -7 is the most frequent abnormality in secondary myeloid disorders, found in 51% of the cases in a series of 246 cases, while del(7q) was found in 7%, and a partial monosomy 7 as a result of an unbalanced translocation in 8% of cases; in contrast, -7/del(7q) is found in 10% of de novo myeloid disorders; the sex ratio is 1.5 male for 1 female; the proportion of adults with a -7 myeloid disorder grows dramatically after 60 years

    Clinics

    characterized by infectious susceptibility, quick aggravation, and treatment resistance

    Prognosis

    monosomy 7 is classified as a poor prognostic criterium by the International Prognostic Scoring System; the actuarial relapse rate at one year is 82 %, and the 7-yr actuarial event-free survival is 6 %; after an allogeneic bone marrow transplantation, -7 is predictive of an unfavorable outcome

    Cytogenetics

    Cytogenetics morphological

    deletion (7q) is always interstitial; 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

    -5/del(5q), found in 40 to 60 % of the secondary MDS cases; 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 not only frequent in secondary MDS or AML, but 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) in childhood blood malignancies exhibits a specific pattern of pathogenesis; chromosome 7 anomalies are not rare in acute lymphocytic leukaemia (ALL); they occur in balanced translocations involving 7p15 or 7q34 in T lineage and 7q22 or 7q32 in B proliferations; monosomy 7 is present in 5 to 6 % of ALL, most often as a secondary anomaly of the t(9;22); the association t(9;22), -7 is present in 16 % of the Ph1+ ALL, i.e. in 3% of ALL as a whole; we will hereunder focuse on -7/del(7q) in adult myeloproliferations
    Atlas Image
    del(7q)  Figure 1: Partial karyotypes with 7q deletions (A). Fluorescence in situ hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing  2 green and 2 red signals on normal and one red signal in abnormal metaphases indicating 7q deletion of various sizes (C-H) u2013 Courtesy Adriana Zamecnikova. Figure 2: del(7q) G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen; Hybridization with Vysis D7S486 (7q31)/CEP 7 probe (Abbott moleculars, US) showing 1 green and 1 red signal confirming monosomy 7on metaphase and interphase cells u2013 Courtesy Adriana Zamecnikova.

    Citation

    François Desangles

    -7/del(7q) in adults

    Atlas Genet Cytogenet Oncol Haematol. 1999-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/1093/cancer-prone-explorer/