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+21 or trisomy 21

Written2001-08Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1041
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.
 
  Ring(21) and dicentric(21) chromosomes, G-banding - Courtesy Elise Labis.

Clinics and Pathology

Disease Acute myeloid leukemia (AML) / myelodysplastic syndromes (MDS)
Phenotype / cell stem 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).
  • 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.

  • Disease Acute lymphocytic leukemia (ALL)
    Phenotype / cell stem 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.
  • 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 a favorable prognosis.
  • 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.
  • Genetics

  • 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.
  • Bibliography

    Acute lymphoblastic leukemia and chromosome 21.
    Berger R
    Cancer genetics and cytogenetics. 1997 ; 94 (1) : 8-12.
    PMID 9078285
     
    Clinical and prognostic significance of trisomy 21 in adult patients with acute myelogenous leukemia and myelodysplastic syndromes.
    Cortes JE, Kantarjian H, O'Brien S, Keating M, Pierce S, Freireich EJ, Estey E
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (1) : 115-117.
    PMID 7845005
     
    Hematologic disorders in 13 patients with acquired trisomy 21 and 13 individuals with Down syndrome.
    Dewald GW, Diez-Martin JL, Steffen SL, Jenkins RB, Stupca PJ, Burgert EO Jr
    American journal of medical genetics. Supplement. 1990 ; 7 : 247-250.
    PMID 2149957
     
    Trisomy 21 is a recurrent secondary aberration in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion.
    Loncarevic IF, Roitzheim B, Ritterbach J, Viehmann S, Borkhardt A, Lampert F, Harbott J
    Genes, chromosomes & cancer. 1999 ; 24 (3) : 272-277.
    PMID 10451708
     
    Trisomy 21 in neoplastic cells.
    Mitelman F, Heim S, Mandahl N
    American journal of medical genetics. Supplement. 1990 ; 7 : 262-266.
    PMID 2149959
     
    Trisomy 21 as the sole acquired chromosomal abnormality in children with acute lymphoblastic leukemia.
    Raimondi SC, Pui CH, Head D, Behm F, Privitera E, Roberson PK, Rivera GK, Williams DL
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1992 ; 6 (3) : 171-175.
    PMID 1533007
     
    Trisomy 21 as the sole acquired karyotypic abnormality in acute myeloid leukemia and myelodysplastic syndrome.
    Wan TS, Au WY, Chan JC, Chan LC, Ma SK
    Leukemia research. 1999 ; 23 (11) : 1079-1083.
    PMID 10576514
     
    Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602).
    Watson MS, Carroll AJ, Shuster JJ, Steuber CP, Borowitz MJ, Behm FG, Pullen DJ, Land VJ
    Blood. 1993 ; 82 (10) : 3098-3102.
    PMID 8219201
     
    Trisomy 21 in acute myeloid leukemia.
    Wei CH, Yu IT, Tzeng CH, Fan FS, Hsieh RK, Chiou TJ, Liu JH, Chen PM
    Cancer genetics and cytogenetics. 1996 ; 86 (2) : 177-180.
    PMID 8603351
     

    Citation

    This paper should be referenced as such :
    Viguié, F
    +21 or trisomy 21
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):294-295.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/tri21ID1041.html


    Other genes implicated (Data extracted from papers in the Atlas) [ 5 ]

    Genes ABL1 BCR FGFR1 GATA1 RARA

    External links

    arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMapTopo ( C42) Morph ( 9861/3) - 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+21 or trisomy 21
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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