Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia

Author:

Santamaría Carlos M.12,Chillón María C.1,García-Sanz Ramón12,Pérez Cristina3,Caballero María D.1,Ramos Fernando4,de Coca Alfonso García5,Alonso José M.6,Giraldo Pilar7,Bernal Teresa8,Queizán José A.9,Rodriguez Juan N.10,Fernández-Abellán Pascual11,Bárez Abelardo12,Peñarrubia María J.13,Balanzategui Ana1,Vidriales María B.1,Sarasquete María E.1,Alcoceba Miguel1,Díaz-Mediavilla Joaquín3,San Miguel Jesús F.12,Gonzalez Marcos12

Affiliation:

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

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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