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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1575-1583.
Prepublished online as a Blood First Edition Paper on October 30, 2007; DOI 10.1182/blood-2007-09-114231.
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NEOPLASIA
Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study
Erik Forestier1,
Shai Izraeli2,
Berna Beverloo3,
Oskar Haas4,
Andrea Pession5,
Kyra Michalová6,
Batia Stark7,
Christine J. Harrison8,
Andrea Teigler-Schlegel9, and
Bertil Johansson10
1 Pediatrics Unit, Department of Clinical Sciences, University of Umeå, Umeå, Sweden;
2 Department of Pediatric Hemato-Oncology, Cancer Research Center, Safra's Children's Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;
3 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands;
4 Department of Pediatric Hematology and Oncology and Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria;
5 Department of Pediatrics, University of Bologna, San Orsola Hospital, Bologna, Italy;
6 Center of Oncocytogenetics Institute of Clinical Biochemistry and Laboratory Diagnostics, General Faculty Hospital and 1st Medical Faculty, Charles University, Prague, Czech Republic;
7 Department of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel;
8 Leukaemia Research Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom;
9 Oncogenetic Laboratory, Department of Human Genetics, Giessen, Germany; and
10 Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
Children with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALLs and 189 DS-AMLs. Unlike previous smaller series, a significant proportion of DS-ALLs had the typical B-cell precursor ALL abnormalities high hyperdiploidy (HeH; 11%) and t(12;21)(p13;q22) (10%). The HeH DS-ALLs were characterized by gains of the same chromosomes as non–DS-HeH, suggesting the same etiology/pathogenesis. In addition, specific genetic subtypes of DS-ALL were suggested by the significant overrepresentation of cases with +X, t(8;14)(q11;q32), and del(9p). Unlike DS-ALL, the common translocations associated with non–DS-AML were rare in DS-AML, which instead were characterized by the frequent presence of dup(1q), del(6q), del(7p), dup(7q), +8, +11, del(16q), and +21. This series of DS leukemias—the largest to date—reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities. Furthermore, this analysis confirms that DS-AML is a distinct entity, originating through other genetic pathways than do non–DS-AMLs, and suggests that unbalanced changes such as dup(1q), +8, and +21 are involved in the leukemogenic process.
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