High FOXO3a expression is associated with a poorer prognosis in AML with normal cytogenetics.
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>50x10(9)/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.
Santamaría
Carlos M
CM
Hospital Universitario, Salamanca, Spain; Centro de Investigación Del Cáncer-IBMCC (USAL-CSIC) of Salamanca, Spain. cmsantamaria@usal.es
Chillón
Maria C
MC
García-Sanz
Ramón
R
Pérez
Cristina
C
Caballero
María D
MD
Ramos
Fernando
F
de Coca
Alfonso García
AG
Alonso
José M
JM
Giraldo
Pilar
P
Bernal
Teresa
T
Queizán
José A
JA
Rodriguez
Juan N
JN
Fernández-Abellán
Pascual
P
Bárez
Abelardo
A
Peñarrubia
María J
MJ
Vidriales
María B
MB
Balanzategui
Ana
A
Sarasquete
María E
ME
Alcoceba
Miguel
M
Díaz-Mediavilla
Joaquín
J
San Miguel
Jesús F
JF
Gonzalez
Marcos
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult
C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt