Single-nucleotide polymorphism array-based karyotyping of acute promyelocytic leukemia

PLoS One. 2014 Jun 24;9(6):e100245. doi: 10.1371/journal.pone.0100245. eCollection 2014.

Abstract

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), but additional chromosomal abnormalities (ACA) and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A) 6.0 (Affymetrix) in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%): 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH), being a duplication of 8(q24) (23%) and a deletion of 7(q33-qter) (6%) the most frequent copy-number abnormalities (CNA). Four patients (8%) showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24) and del(7q33-qter), ACA were infrequent (≤3%) but most of them recurrent (70%). Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17) that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 15
  • Chromosomes, Human, Pair 17
  • Female
  • Humans
  • Karyotyping*
  • Leukemia, Promyelocytic, Acute / diagnosis
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / mortality
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Translocation, Genetic
  • Young Adult

Substances

  • Oncogene Proteins, Fusion

Grants and funding

This work was supported by the Grant “Rio Hortega” (CM10/00321, CM11/00343), the Health Research Program (PI12/01047), the program “Red Temática de Investigación Cooperativa en Cáncer” (RD12/0036/0014) and the “Red Cooperativa de Biobancos Hospitalarios” (RD09/0076/00021) from “Instituto de Salud Carlos III”, Ministry of Science and Innovation, Spain, (www.isciii.es); the research grant 2013/0327 from the “Instituto Investigación Sanitaria Hospital La Fe”, (www.iislafe.es); and the Excellence Research Project (PROMETEO/2011/025) granted by Generalitat Valenciana, (www.cece.gva.es). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.