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. 2014 May;28(5):1015-21.
doi: 10.1038/leu.2013.317. Epub 2013 Oct 29.

An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

C J Harrison  1 , A V Moorman  1 , C Schwab  1 , A J Carroll  2 , E A Raetz  3 , M Devidas  4 , S Strehl  5 , K Nebral  5 , J Harbott  6 , A Teigler-Schlegel  6 , M Zimmerman  7 , N Dastuge  8 , A Baruchel  9 , J Soulier  10 , M-F Auclerc  9 , A Attarbaschi  5 , G Mann  5 , B Stark  11 , G Cazzaniga  12 , L Chilton  1 , P Vandenberghe  13 , E Forestier  14 , I Haltrich  15 , S C Raimondi  16 , M Parihar  17 , J-P Bourquin  18 , J Tchinda  18 , C Haferlach  19 , A Vora  20 , S P Hunger  21 , N A Heerema  22 , O A Haas  5 ; Ponte di Legno International Workshop in Childhood Acute Lymphoblastic Leukemia
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An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome

C J Harrison et al. Leukemia. 2014 May.

Abstract

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Circos plots showing the relative distribution of the significant copy number changes in a comparator cohort of childhood BCP-ALL (a) and iAMP21 patients (b). In both (a) and (b) the black bar indicates the proportion of patients in which a copy number abnormality (CNA) was detected compared to the proportion without (grey bar). The proportions of CNA affecting the genes tested are colour coded as indicated. PAR1 deletions represent P2RY8-CRLF2.
Figure 2
Figure 2
Kaplan–Meier survival graph showing the EFS and OS of 283 patients with iAMP21.
Figure 3
Figure 3
Kaplan–Meier survival graph showing the proportion of iAMP21 surviving event free according to whether or not they were treated as high risk on their respective protocols.
Figure 4
Figure 4
Kaplan–Meier survival graph showing the proportion of iAMP21 surviving event free according to whether or not they were classified as NCI-SR (<10 years old and WCC <50 × 109/l) or NCI-HR (≥ 10years old or WCC >50 × 109/l).
See this image and copyright information in PMC

References

    1. Harewood L, Robinson H, Harris R, Al Obaidi MJ, Jalali GR, Martineau M, et al. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia. 2003;17:547–553. - PubMed
    1. Soulier J, Trakhtenbrot L, Najfeld V, Lipton JM, Mathew S, Avet-Loiseau H, et al. Amplification of band q22 of chromosome 21, including AML1, in older children with acute lymphoblastic leukemia: an emerging molecular cytogenetic subgroup. Leukemia. 2003;17:1679–1682. - PubMed
    1. Alvarez Y, Coll MD, Bastida P, Ortega JJ, Caballin MR. AML1 amplification in a child with acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2003;140:58–61. - PubMed
    1. Dube ID, el Solh H. An apparent tandem quadruplication of chromosome 21 in a case of childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 1986;23:253–256. - PubMed
    1. Le Coniat M, Romana SP, Berger R. Partial chromosome 21 amplification in a child with acute lymphoblastic leukemia. Genes Chromosomes Cancer. 1995;14:204–209. - PubMed

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