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BAALC is an important predictor of refractoriness to chemotherapy and poor survival in intermediate-risk acute myeloid leukemia (AML)

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Abstract

We have analyzed brain and acute leukemia, cytoplasmic (BAALC) gene expression and other genetic markers (ERG, EVI1, MN1, PRAME, WT1, FLT3, and NPM1 mutations) in 127 intermediate-risk acute myeloid leukemia (AML) patients: 98 cytogenetically normal and 29 with intermediate-risk cytogenetic alterations. High versus low BAALC expressers showed a higher refractoriness to induction treatment (31% vs 10%; p = .005), lower complete remission rate after salvage therapy (82% vs 97%; p = .010), and lower 3-year overall (23% vs 58%, p < .001) and relapse-free survival (26% vs 52%, p = .006). Similar results were found when cytogenetic subgroups were analyzed separately. Multivariate models confirmed the unfavorable prognosis of this marker. In conclusion, BAALC is a relevant prognostic marker in intermediate-risk AML.

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Acknowledgements

The authors would like to thank the Spanish cooperative group PETHEMA (Program for the Study and Treatment of Malignant Hemopathies) for providing the treatment protocol, samples, and clinical information. This work has been partially supported by the grants PI061351 and 00/0023-00 from the Spanish “Fondo de Investigaciones Sanitarias de la Seguridad Social”, 89/A/06 from “Gerencia Regional de Salud, Junta Castilla y León”, and CIC, IBMCC (USAL-CSIC), Spain.

Author's contributions

Santamaría C. and Chillón M. C. carried out all molecular studies and prepared the database for the final analysis. Santamaría C. performed the statistical analysis and prepared the initial version of the paper.

Garcia-Sanz R. helped in the design of the work, reviewed the database, and contributed towards the statistical analysis. He provided the pre-approval of the final version.

Pérez C., Caballero D., Mateos M. V., Ramos F., García de Coca A., Alonso J. M., Giraldo P., Bernal T., Queizán J. A., Rodriguez J. N., and Díaz-Mediavilla J. were the clinicians responsible for the patients and those who ensured the application of protocol, sampling, and the collection of clinical data.

Puig N., Balanzategui A., Sarasquete M. E., and Alcoceba M. participated in the generation of the molecular results.

San Miguel J. F. and González M. initially promoted the study and were responsible for securing financial support. Both were responsible for the group and were the persons responsible for the most important revision of the draft. González M. was the person who approved the final version to be sent to the editor.

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Authors and Affiliations

  1. Hospital Universitario, Salamanca, Spain

    Carlos Santamaría, María C. Chillón, Ramón García-Sanz, María D. Caballero, María V. Mateos, Noemí Puig, Ana Balanzategui, María E. Sarasquete, Miguel Alcoceba, Jesús San Miguel & Marcos González

  2. Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

    Carlos Santamaría, Ramón García-Sanz, Jesús San Miguel & Marcos González

  3. Hospital Clínico San Carlos, Madrid, Spain

    Cristina Pérez & Joaquín Díaz-Mediavilla

  4. Complejo Hospitalario de León and Ibiomed, León, Spain

    Fernando Ramos

  5. Hospital Clínico de Valladolid, Valladolid, Spain

    Alfonso García de Coca

  6. Hospital Río Carrión de Palencia, Palencia, Spain

    José M. Alonso

  7. Hospital Miguel Servet, Zaragoza, Spain

    Pilar Giraldo

  8. Hospital Central de Asturias, Oviedo, Spain

    Teresa Bernal

  9. Hospital General de Segovia, Segovia, Spain

    José A. Queizán

  10. Hospital Juan Ramón Jiménez, Huelva, Spain

    Juan N. Rodríguez

  11. Department of Hematology, University Hospital of Salamanca, Paseo de San Vicente, 58-182, Salamanca, 37007, Spain

    Carlos Santamaría

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  1. Carlos Santamaría
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  2. María C. Chillón
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  18. Joaquín Díaz-Mediavilla
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  19. Jesús San Miguel
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  20. Marcos González
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Corresponding author

Correspondence to Carlos Santamaría.

Electronic supplementary material

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Supplementary Table 1

Abnormal karyotypes of AML patients included in the study (DOC 74 kb)

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Santamaría, C., Chillón, M.C., García-Sanz, R. et al. BAALC is an important predictor of refractoriness to chemotherapy and poor survival in intermediate-risk acute myeloid leukemia (AML). Ann Hematol 89, 453–458 (2010). https://doi.org/10.1007/s00277-009-0864-x

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  • DOI: https://doi.org/10.1007/s00277-009-0864-x

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