PLoS ONE (Jan 2014)

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

  • Inés Gómez-Seguí,
  • Dolors Sánchez-Izquierdo,
  • Eva Barragán,
  • Esperanza Such,
  • Irene Luna,
  • María López-Pavía,
  • Mariam Ibáñez,
  • Eva Villamón,
  • Carmen Alonso,
  • Iván Martín,
  • Marta Llop,
  • Sandra Dolz,
  • Oscar Fuster,
  • Pau Montesinos,
  • Carolina Cañigral,
  • Blanca Boluda,
  • Claudia Salazar,
  • Jose Cervera,
  • Miguel A Sanz

DOI
https://doi.org/10.1371/journal.pone.0100245
Journal volume & issue
Vol. 9, no. 6
p. e100245

Abstract

Read online

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.