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Chronic Lymphocytic Leukemia

Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation

Leukemia volume 21, pages 1984–1991 (2007)Cite this article

Abstract

Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment. First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-κB1 (NF-κB1). The expression of these clusters identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-κB clusters, which can be used to predict time to treatment in early clinical stages.

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Acknowledgements

We thank the Tumour Bank Network of the CNIO for the coordination of shipment of samples. Francisco Cifuentes is a full-time employee of the company Agilent Technologies, whose custom product ‘8-pack microarray’ platform was used in the present study.

Author information

Authors and Affiliations

  1. Molecular Pathology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain

    A Rodríguez, R Villuendas, P de la Cueva, M C Marín, A Swat & M A Piris

  2. Hematology Department, Hospital Marqués de Valdecilla, Santander, Spain

    L Yáñez, M A Cuadrado & E Conde

  3. Hematology Department, Hospital Gregorio Marañón, Madrid, Spain

    M E Gómez & N Hernández

  4. Bioinformatic Program, Spanish National Cancer Centre (CNIO), Madrid, Spain

    R Díaz

  5. National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain

    M Pollán

  6. Genetics and Pathology Department, Hospital Virgen de la Salud, Toledo, Spain

    E Ruiz

  7. Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain

    L Lombardía

  8. Agilent Technologies, Palo Alto, CA, USA

    F Cifuentes

  9. Hematology Department, Hospital Clínico Universitario, Salamanca, Spain

    M Gonzalez

  10. Hematology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain

    J A García-Marco

Authors
  1. A Rodríguez
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  2. R Villuendas
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  13. E Conde
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  14. L Lombardía
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  16. M Gonzalez
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for Spanish National Cancer Centre (CNIO)

Corresponding author

Correspondence to M A Piris.

Additional information

Financial support: This study was supported by grants from the Ministerio de Sanidad y Consumo (G03/179, PI051623) and the Ministerio de Ciencia y Tecnología (SAF2005-00221, SAF2004-04286), Spain. Antonia Rodríguez was supported by a grant from the Asociación Española Contra el Cáncer (AECC).

Supplementary Information accompanies the paper on the Leukemia web site (http://www.nature.com/leu)

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Rodríguez, A., Villuendas, R., Yáñez, L. et al. Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation. Leukemia 21, 1984–1991 (2007). https://doi.org/10.1038/sj.leu.2404831

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