title: An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome.
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.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Moorman
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: C
authors.initials: C
authors.lastname: Schwab
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Carroll
authors.affiliation: The New York University Cancer Institute, New York University Langone Medical Center, New York, NY, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Raetz
authors.affiliation: University of Florida, Gainesville, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Devidas
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Strehl
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Nebral
authors.affiliation: Department of Paediatric Haematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.affiliation: Department of Paediatric Haematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.affiliation: Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zimmerman
authors.affiliation: Laboratoire d'hématologie, Génétique des Hémopathies, Hôpital Purpan, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Dastuge
authors.affiliation: Pediatric Hematology-Immunology, Hôpital Robert Debré (AP-HP), Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: Saint-Louis hospital APHP and Hematology University Institute (IUH), University Paris-Diderot, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Soulier
authors.affiliation: Pediatric Hematology-Immunology, Hôpital Robert Debré (AP-HP), Paris, France.
authors.forename: M-F
authors.initials: MF
authors.lastname: Auclerc
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.affiliation: Pediatric Hemato/Oncology Center, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Stark
authors.affiliation: Centro Ricerca Tettamanti, Clinica Pediatrica, University of Milano-Bicocca, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cazzaniga
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: L
authors.identifier: 0000000235595644
authors.initials: L
authors.lastname: Chilton
authors.affiliation: Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Vandenberghe
authors.affiliation: Department of Medical Biosciences, Genetics, Umeå University Hospital, Umeå, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Forestier
authors.affiliation: Departments of Pediatrics, Semmelweis University of Medicine, Budapest, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Haltrich
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Raimondi
authors.affiliation: Department of Cytogenetics and Laboratory Hematology Tata Medical Center, Kolkata, West Bengal, India.
authors.forename: M
authors.initials: M
authors.lastname: Parihar
authors.affiliation: Department of Oncology and Children's Research Center, University Hospital Zurich, Zurich, Switzerland.
authors.forename: J-P
authors.initials: JP
authors.lastname: Bourquin
authors.affiliation: Department of Oncology and Children's Research Center, University Hospital Zurich, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Tchinda
authors.affiliation: MLL, Munich Leukemia Laboratory, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Haferlach
authors.affiliation: Sheffield Children's Hospital, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Vora
authors.affiliation: Children's Hospital Colorado, and University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Hunger
authors.affiliation: Department of Pathology, Ohio State University, Columbus, OH, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human