Haematologica (May 2010)

Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients

  • María Carmen Chillón,
  • Carlos Santamaría,
  • Ramón García-Sanz,
  • Ana Balanzategui,
  • Sarasquete María Eugenia,
  • Miguel Alcoceba,
  • Luis Marín,
  • María Dolores Caballero,
  • María Belén Vidriales,
  • Fernando Ramos,
  • Teresa Bernal,
  • Joaquín Díaz-Mediavilla,
  • Alfonso García de Coca,
  • María Jesús Peñarrubia,
  • José Antonio Queizán,
  • Pilar Giraldo,
  • Jesús F. San Miguel,
  • Marcos González

DOI
https://doi.org/10.3324/haematol.2009.015073
Journal volume & issue
Vol. 95, no. 5

Abstract

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Background Internal tandem duplications of the FLT3 gene (FLT3-ITDs) are frequent in patients with acute promyelocytic leukemia (APL), however its clinical impact remains controversial.Design and Methods We analyzed the prognostic significance of FLT3-ITD mutant level and size, as well as FLT3-D835 point mutations, PML-RARα expression and other predictive factors in 129 APL patients at diagnosis enrolled on the Spanish LPA96 (n=43) or LPA99 (n=86) PETHEMA trials.Results FLT3-ITDs and D835 mutations were detected in 21% and 9% of patients, respectively. Patients with increased ITD mutant/wild-type ratio or longer ITD size displayed shorter 5-year relapse-free survival (RFS) (P=0.048 and P