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 Blood, 2 July 2009, Vol. 114, No. 1, pp. 148-152.
Prepublished online as a Blood First Edition Paper on April 27, 2009; DOI 10.1182/blood-2008-11-187724.

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MYELOID NEOPLASIA

Brief report

Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia

Carlos M. Santamaría1,2, María C. Chillón1, Ramón García-Sanz1,2, Cristina Pérez3, María D. Caballero1, Fernando Ramos4, Alfonso García de Coca5, José M. Alonso6, Pilar Giraldo7, Teresa Bernal8, José A. Queizán9, Juan N. Rodriguez10, Pascual Fernández-Abellán11, Abelardo Bárez12, María J. Peñarrubia13, Ana Balanzategui1, María B. Vidriales1, María E. Sarasquete1, Miguel Alcoceba1, Joaquín Díaz-Mediavilla3, Jesús F. San Miguel1,2, and Marcos Gonzalez1,2

1 Hospital Universitario, Salamanca; 2 Centro de Investigación del Cáncer-Instituto de Biologia Molecular y Celular del Cancer (Universidad de Salamanca-Consejo Superior de Investigaciones Cientificas), Salamanca; 3 Hospital Clínico San Carlos, Madrid; 4 Complejo Hospital de León and Ibiomed, Universidad de León, León; 5 Hospital Clínico de Valladolid, Valladolid; 6 Hospital Río Carrión de Palencia, Palencia; 7 Hospital Miguel Servet, Zaragoza; 8 Hospital Central de Asturias, Oviedo; 9 Hospital General de Segovia, Segovia; 10 Hospital Juan Ramón Jiménez, Huelva; 11 Hospital Universitario de Alicante, Alicante; 12 Hospital Nuestra Señora de Sonsoles, Ávila; and 13 Hospital Río Hortega, Valladolid, Spain

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.


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