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Leukemia. 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.

Author information

1
Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
2
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
3
The New York University Cancer Institute, New York University Langone Medical Center, New York, NY, USA.
4
University of Florida, Gainesville, FL, USA.
5
Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
6
Department of Paediatric Haematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany.
7
Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany.
8
Laboratoire d'hématologie, Génétique des Hémopathies, Hôpital Purpan, Toulouse, France.
9
Pediatric Hematology-Immunology, Hôpital Robert Debré (AP-HP), Paris, France.
10
Saint-Louis hospital APHP and Hematology University Institute (IUH), University Paris-Diderot, Paris, France.
11
Pediatric Hemato/Oncology Center, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel.
12
Centro Ricerca Tettamanti, Clinica Pediatrica, University of Milano-Bicocca, Milan, Italy.
13
Center for Human Genetics, University of Leuven, Leuven, Belgium.
14
Department of Medical Biosciences, Genetics, Umeå University Hospital, Umeå, Sweden.
15
Departments of Pediatrics, Semmelweis University of Medicine, Budapest, Hungary.
16
Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
17
Department of Cytogenetics and Laboratory Hematology Tata Medical Center, Kolkata, West Bengal, India.
18
Department of Oncology and Children's Research Center, University Hospital Zurich, Zurich, Switzerland.
19
MLL, Munich Leukemia Laboratory, Munich, Germany.
20
Sheffield Children's Hospital, Sheffield, UK.
21
Children's Hospital Colorado, and University of Colorado School of Medicine, Aurora, CO, USA.
22
Department of Pathology, Ohio State University, Columbus, OH, USA.

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.

PMID:
24166298
PMCID:
PMC4283797
DOI:
10.1038/leu.2013.317
[Indexed for MEDLINE]
Free PMC Article

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