+21 or trisomy 21

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

+21 or trisomy 21

Identity

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.

Clinics and Pathology

Disease Acute non lymphocytic leukemia (ANLL) / myelodysplastic syndromes (MDS)

Phenotype / cell stem origin no specific phenotype but possibly a slight higher incidence in monocytic phenotypes (ANLL-M4 and M5, chronic myelomonocytic leukemia (CMML)). ANLL-M7 with acquired +21 is exceptional , whereas ANLL-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 aneuploīdy 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 ANLL 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 ANLL patients. This has not been confirmed in acquired trisomy 21.

External links

Other database +21 or trisomy 21 Mitelman database (CGAP - NCBI)

Other database	+21 or trisomy 21	Mitelman database (CGAP - NCBI)

Bibliography

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 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 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

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

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

Acute lymphoblastic leukemia and chromosome 21.

Berger R

Cancer genetics and cytogenetics. 1997 ; 94 (1) : 8-12.

PMID 9078285

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 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

Contributor(s)

Written 08-2001 Franck Viguié

Citation

This paper should be referenced as such :
Viguié F . +21 or trisomy 21. Atlas Genet Cytogenet Oncol Haematol. August 2001 .
URL : http://AtlasGeneticsOncology.org/Genes/tri21ID1041.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Dec 6 18:03:43 2008

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.

Disease	Acute non lymphocytic leukemia (ANLL) / myelodysplastic syndromes (MDS)
Phenotype / cell stem origin	no specific phenotype but possibly a slight higher incidence in monocytic phenotypes (ANLL-M4 and M5, chronic myelomonocytic leukemia (CMML)). ANLL-M7 with acquired +21 is exceptional , whereas ANLL-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 aneuploīdy 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.