DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups

• Published in: Leukemia Vol. 21; no. 6; pp. 1224 - 1231
• Main Authors: SUELA, J, ALVAREZ, S, CALASANZ, M. J, CIGUDOSA, J. C, CIFUENTES, F, LARGO, C, FERREIRA, Bl, BLESA, D, ARDANAZ, M, GARCIA, R, MARQUEZ, J. A, ODERO, M. D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.06.2007; Nature Publishing Group
• Subjects: Aberration; Acute Disease; Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bone Marrow; Cancer; Copy number; Cytogenetic Analysis; Cytogenetics; Deletion; Deoxyribonucleic acid; DNA; DNA fingerprinting; Gene Dosage; Gene polymorphism; Genomes; Genomic Instability; Hematologic and hematopoietic diseases; Hematology; Humans; Karyotypes; Kinases; Leukemia; Leukemia, Myeloid - diagnosis; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes; Medical prognosis; Medical sciences; Middle Aged; Mutation; Oligonucleotide Array Sequence Analysis; Prognosis; Risk; Risk groups; Software; Statistical analysis; Statistical methods; United States > US; Madrid Spain; Spain; Chromosomal aberration; Prognosis; Hematology; array CGH; Malignant hemopathy; Genetic instability; De novo; acute myeloid leukemia; Lymphoproliferative syndrome; DNA; C-Onc gene; Cytogenetics; cytogenetic prognosis; Genetics; Acute lymphocytic leukemia; Array-based Comparative Genomic Hybridisation; Protooncogene; Acute myelocytic leukemia; FLT3 ITD
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2404653

We have carried out a high-resolution whole genome DNA profiling analysis on 100 bone marrow samples from a consecutive series of de novo acute myeloid leukemia (AML) cases. After discarding copy number changes that are known to be genetic polymorphisms, we found that genomic aberrations (GA) in the form of gains or losses of genetic material were present in 74% of the samples, with a median of 2 GA per case (range 0-35). In addition to the cytogenetically detected aberration, GA were present in cases from all cytogenetic prognostic groups: 79% in the favorable group, 60% in the intermediate group (including 59% of cases with normal karyotype) and 83% in the adverse group. Five aberrant deleted regions were recurrently associated with cases with a highly aberrant genome (e.g., a 1.5 Mb deletion at 17q11.2 and a 750 kb deletion at 5q31.1). Different degrees of genomic instability showed a statistically significant impact on survival curves, even within the normal karyotype cases. This association was independent of other clinical and genetic parameters. Our study provides, for the first time, a detailed picture of the nature and frequency of DNA copy number aberrations in de novo AML.