+21 or trisomy 21

2001-08-01   Franck Viguié  

Clinics and Pathology

Disease

Acute myeloid leukemia (AML) / myelodysplastic syndromes (MDS)

Phenotype stem cell origin

No specific phenotype but possibly a slight higher incidence in monocytic phenotypes (AML-M4 and -M5, chronic myelomonocytic leukemia (CMML)). AML-M7 with acquired +21 is exceptional , whereas AML-M7 is frequent in Down Syndrome.

Epidemiology

  • +21 is the second more frequent acquired trisomy, after trisomy 8, in adult ANNL/MDS. It is rarely observed as the sole abnormality. According to large series, +21 was observed in 3% to 7% of cases, out of which 0.3-0.4% of cases with +21 as the only abnormality.
  • The more frequent association is with -5/5q- and -7/7q-, followed by trisomy 8 and structural rearrangements t(8;21), t(15;17) and inv(16).
  • Alternatively to +21 and in the same clinical context, tetrasomy or pentasomy 21 can be observed, as well as single or multiple copies of a structuraly rearranged chromosome 21, such as i(21q), psu dic(21q) or r(21). In some of these der(21), a chromosome 21 segment can be tandemly amplified as homogeneous staining region (HSR). , 
  • As the sole clonal abnormality (excepting DS patients), +21 accounts for 2% of pediatric and less than 1% of adult ALL cases. , 
  • In childhood ALL, the incidence of +21 is approximately of 40% and of 80%, respectively, in the 47-50 chromosomes and in the > 50 chromosomes ploidy groups. , 
  • The main association is with t(12;21)(p13;q22) in childhood (15% of cases at diagnosis), followed by 6q abnormalities. Association also with t(1;19)(q23;p13), t(4;11)(q21;q23) and 14q abnormalities. , 
  • The main association with a second aneuploidy is with +X, +16 or -20. , 
  • In adults, +21 is associated the most frequently with t(9;22)(q34;q11): about 50% of cases.

    • Prognosis

  • +21 as sole abnormality has an unfavorable prognosis, none of the published patients could achieve a long-term disease-free survival.
  • When associated with other recurrent chromosome changes, it does not modify the prognosis of these abnormalities. , 
  • In the group 47-50 chromosomes, + 21 has a rather good prognosis in children, when it is not associated with a bad prognosis structural rearrangement. In the same ploidy group, +21 has no prognostic impact in adults.

    • Disease

    Acute lymphocytic leukemia (ALL)

    Phenotype stem cell origin

    Essentially B-cell lineage.

    Epidemiology

  • +21 is the more frequent aneuploïdy observed in both adult and childhood ALL. Its overall incidence would be around 15% of cases.

    • Prognosis

  • +21 as sole abnormality has a favorable prognosis.

    • Note

  • Gene(s) involved in trisomy 21 associated leukemia is (are) unknown.
  • The 21q22 region seems crucial. Der(21) containing an HSR have constantly multiple copies tandemly amplified of the AML1 gene, both in AML and in ALL, but there is no proof that this gene is directely implicated.
  • The overexpression of cystathionine-b-synthetase (CBS; 21q22.3) would be linked to increased sensitivity of myeloblasts to ara-C and daunorubicin in DS AML patients. This has not been confirmed in acquired trisomy 21.

    • Genes Involved and Proteins

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    90782851997Acute lymphoblastic leukemia and chromosome 21.Berger R et al
    78450051995Clinical and prognostic significance of trisomy 21 in adult patients with acute myelogenous leukemia and myelodysplastic syndromes.Cortes JE et al
    21499571990Hematologic disorders in 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome.Dewald GW et al
    104517081999Trisomy 21 is a recurrent secondary aberration in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion.Loncarevic IF et al
    21499591990Trisomy 21 in neoplastic cells.Mitelman F et al
    15330071992Trisomy 21 as the sole acquired chromosomal abnormality in children with acute lymphoblastic leukemia.Raimondi SC et al
    105765141999Trisomy 21 as the sole acquired karyotypic abnormality in acute myeloid leukemia and myelodysplastic syndrome.Wan TS et al
    82192011993Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602).Watson MS et al
    86033511996Trisomy 21 in acute myeloid leukemia.Wei CH et al

    Summary

    Note

    Acquired trisomy 21 is not to be confused with constitutional trisomy 21 (Down syndrome, DS) which is a factor of predisposition to childhood acute leukemia but whose significance and clinical context are quite different.
    Atlas Image
    Trisomy 21 and partial trisomy 21 Top: various chromosome 21 rearrangements with partial trisomy 21: Ring(21) and dicentric(21) chromosomes, G-banding - Courtesy Elise Labis. Bottom: Fluorescence in situ hybridization with the Vysis LSI RUNX1/RUNX1T1 dual color dual fusion and LSI ETV6 /RUNX1probes (Abbott Molecular, US) showing 3 copies (green signals) (A) and 4 copies of chromosomes 21 (red signals) (B) - Courtesy Adriana Zamecnikova.

    Citation

    Franck Viguié

    +21 or trisomy 21

    Atlas Genet Cytogenet Oncol Haematol. 2001-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1041/+21-or-trisomy-21