High FOXO3a expression is associated with a poorer prognosis in AML with normal cytogenetics

• Published in: Leukemia research Vol. 33; no. 12; pp. 1706 - 1709
• Main Authors: Santamaría, Carlos M, Chillón, Maria C, García-Sanz, Ramón, Pérez, Cristina, Caballero, María D, Ramos, Fernando, de Coca, Alfonso García, Alonso, José M, Giraldo, Pilar, Bernal, Teresa, Queizán, José A, Rodriguez, Juan N, Fernández-Abellán, Pascual, Bárez, Abelardo, Peñarrubia, María J, Vidriales, María B, Balanzategui, Ana, Sarasquete, María E, Alcoceba, Miguel, Díaz-Mediavilla, Joaquín, San Miguel, Jesús F, Gonzalez, Marcos
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2009
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Aged; AKT; Female; Forkhead Box Protein O3; Forkhead Transcription Factors - genetics; FOXO3a; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Humans; Leukemia, Myeloid, Acute - enzymology; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Male; Middle Aged; Phosphatidylinositol 3-Kinases - metabolism; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; Real time quantitative PCR; Survival Analysis; Young Adult; Real time quantitative PCR; AKT; FOXO3a; Acute myeloid leukemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2009.04.024

Abstract The PI3/AKT pathway is up-regulated in acute myeloid leukemia (AML), but its prognostic relevance in cytogenetically normal AML (CN-AML) is unclear. We evaluated RNA levels of AKT and two downstream substrates ( FOXO3a-p27 ) in 110 de novo CN-AML, included in the Spanish PETHEMA therapeutic protocols. Patients with high FOXO3a gene expression displayed shorter OS ( p = 0.015) and RFS ( p = 0.048) than low FOXO3a expressers. Features selected in the multivariate analysis as having an independent prognostic value for a shorter survival were WBC > 50 × 109 /L, age >65 years and high FOXO3a expression. We concluded that FOXO3a assessment could contribute to improve the molecular-based risk stratification in CN-AML.