Single-Nucleotide Polymorphism Array-Based Karyotyping of Acute Promyelocytic Leukemia

Autores de IIS La Fe

• Inés Gómez Seguí

  Autor

• Maria Dolores Sanchez Izquierdo

  Autor

• Eva Barragán González

  Autor

• Esperanza Such Taboada

  Autor

• Irene Luna Del Valle

  Autor

• María De La Encarnacion Lopez Pavia

  Autor

• Maria Amparo Ibañez Company

  Autor

• Eva Villamon Ribate

  Autor

• Carmen Maria Alonso Prieto

  Autor

• Ivan Martin Castillo

  Autor

• Marta Llop García

  Autor

• Sandra Dolz Giménez

  Autor

• Oscar Fuster Lluch

  Autor

• Pau Montesinos Fernández

  Autor

• Carolina Cañigral Ortiz

  Autor

• Blanca Boluda Pascual

  Autor

• José Vicente Cervera Zamora

  Autor

• Miguel Ángel Sanz Alonso

  Autor

Participantes ajenos a IIS La Fe

• Salazar C

Grupos

• Hematología y Hemoterapia

• Hemostasia, Trombosis, Arteriosclerosis y Biología vascular

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.