Abstract
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.
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Acknowledgements
We thank our colleagues Carmen Mateos (Hospital Virgen del Camino, Pamplona), José Rifon (Clinica Universitaria de Navarra, Pamplona), Maria Jose Najera (Hospital San Millan, Logroño), Filomena Floristan (Hospital Cruces, Bilbao), Maite Zudaire (Hospital de Navarra Pamplona), Gerardo Hermida (Hospital General Yague, Burgos), Angel Pereda (Hospital Santiago, Vitoria), Gemma Azaceta (Hospital Clinico Lozano Blesa, Zaragoza) and Alfonso G. Pineda (Hospital U. Gregorio Marañon, Madrid) for providing samples and clinical information. We also thank M. José Larrayoz and Iria Gonzalez for managing DNA samples; Joaquin Dopazo (Centro Investigacion Principe Felipe, Valencia) for bioinformatic advice; M Carmen Martín, Carmen Carralero and Gloria Soler for their technical support; and Roger Milne (CeGen, CNIO, Madrid) for his help with the multivariate statistical analysis.
Research grants and financial support: This work was partially financed by grant PI040555 from Fondo Investigaciones Sanitarias, Ministerio de Sanidad y Consumo to JCC and a grant from Fundacion Cientifica de la Asociación Española contra el Cáncer to MDO. JS has a PhD fellowship from Ministerio de Educacion y Ciencia. CL has a PhD fellowship from Gobierno de Navarra. BF has a Marie Curie PhD Early Stage Research Training Fellowship.
Contributions: JS, FC, CL and BF performed the laboratory work, JS, SA, DB, and JCC analyzed the data; MA, RG, JAM, MDO and MJC contributed vital new reagents, and collected clinical data; JCC, MJC and SA designed the study; JS and JCC wrote the paper.
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Suela, J., Álvarez, S., Cifuentes, F. et al. DNA profiling analysis of 100 consecutive de novo acute myeloid leukemia cases reveals patterns of genomic instability that affect all cytogenetic risk groups. Leukemia 21, 1224–1231 (2007). https://doi.org/10.1038/sj.leu.2404653
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DOI: https://doi.org/10.1038/sj.leu.2404653
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