Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia.
We have evaluated 9 new molecular markers (ERG, EVI1, MLL-PTD, MN1, PRAME, RHAMM, and WT1 gene-expression levels plus FLT3 and NPM1 mutations) in 121 de novo cytogenetically normal acute myeloblastic leukemias. In the multivariate analysis, high ERG or EVI1 and low PRAME expressions were associated with a shorter relapse-free survival (RFS) and overall survival (OS). A 0 to 3 score was given by assigning a value of 0 to favorable parameters (low ERG, low EVI1, and high PRAME) and 1 to adverse parameters. This model distinguished 4 subsets of patients with different OS (2-year OS of 79%, 65%, 46%, and 27%; P = .001) and RFS (2-year RFS of 92%, 65%, 49%, and 43%; P = .005). Furthermore, this score identified patients with different OS (P = .001) and RFS (P = .013), even within the FLT3/NPM1 intermediate-risk/high-risk subgroups. Here we propose a new molecular score for cytogenetically normal acute myeloblastic leukemias, which could improve patient risk-stratification.
Santamaría
Carlos M
CM
Hospital Universitario, Universidad de Salamanca-Consejo Superior de Investigaciones Cientificas, Salamanca, Spain.
Chillón
María 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
Balanzategui
Ana
A
Vidriales
María B
MB
Sarasquete
María E
ME
Alcoceba
Miguel
M
Díaz-Mediavilla
Joaquín
J
San Miguel
Jesús F
JF
Gonzalez
Marcos
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D011519:Proto-Oncogenes / Q000235:genetics; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071230:Transcriptional Regulator ERG
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D005819:Genetic Markers; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C000716967:NPM1 protein, human; C404944:PRAME protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D000090243:Nucleophosmin