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Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells

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Abstract

Purpose

Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters.

Methods/patients

Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR.

Results

Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux.

Conclusion

Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

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Abbreviations

CLL-B:

Chronic lymphocytic leukemia of B cells

WB:

Western blot

PBMCs:

Peripheral blood mononuclear cells

AP:

Autophagy

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Acknowledgements

We appreciate the helpful collaboration of Dr. Manuel Gerónimo-Pardo and Dr. José Javier García Ramírez. This work was supported by Grants from Fundación Leticia Castillejo Castillo, Ministerio de Economía y Competitividad (SAF2012-30862, SAF2015-64215R to RSP and MJRH) and Sociedad Castellano Manchega de Hematología y Hemoterapia (to JRRM). OR has a contract for access to the Spanish System of Science, Technology and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM). RPS has a predoctoral contract for the training of research staff funded by the University of Castilla-La Mancha (UCLM) (2014/10340). RSP and MJRH Research Institutes, and the work carried out in their laboratories received support from the European Community through the Regional Development Funding Program (FEDER).

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Author notes

  1. O. Roche, M.-J. Ruiz-Hidalgo, and R. Sánchez-Prieto have contributed equally to this work.

Authors and Affiliations

  1. Servicio de Hematología, Complejo Hospitalario Universitario de Albacete, 02006, Albacete, Spain

    J.-R. Romero-Macías, F. Ruiz-Marcos, A. Serrano-Martínez & P. González-Aguado

  2. Laboratorio de Oncología Molecular, Unidad de Medicina Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, 02006, Albacete, Spain

    J.-R. Romero-Macías, R. Pascual-Serra, O. Roche & M.-J. Ruiz-Hidalgo

  3. Unidad Asociada de Biomedicina CSIC-UCLM, 02006, Albacete, Spain

    O. Roche & M.-J. Ruiz-Hidalgo

  4. Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, 02006, Albacete, Spain

    O. Roche & R. Sánchez-Prieto

  5. Lab. 1.5.2, Departamento de Biología del Cáncer, Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), Arturo Duperier, 4, 28029, Madrid, Spain

    B. Belandia & R. Sánchez-Prieto

  6. Unidad Asociada de Biomedicina CSIC-UCLM, 28029, Madrid, Spain

    B. Belandia & R. Sánchez-Prieto

  7. Área de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Castilla-La Mancha, 02006, Albacete, Spain

    M.-J. Ruiz-Hidalgo

Authors
  1. J.-R. Romero-Macías
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  2. R. Pascual-Serra
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  3. O. Roche
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  4. F. Ruiz-Marcos
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  5. A. Serrano-Martínez
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  6. P. González-Aguado
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  7. B. Belandia
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  8. M.-J. Ruiz-Hidalgo
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  9. R. Sánchez-Prieto
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Corresponding author

Correspondence to R. Sánchez-Prieto.

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Conflict of interest

The authors have no competing interests.

Informed consent

Samples from patients and healthy donors were used after obtaining appropriate informed consent.

Ethical statement

This study was approved by the Ethical and Research Committee of the “Complejo Hospitalario Universitario de Albacete”.

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Romero-Macías, JR., Pascual-Serra, R., Roche, O. et al. Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells. Clin Transl Oncol 21, 1280–1285 (2019). https://doi.org/10.1007/s12094-019-02041-x

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  • DOI: https://doi.org/10.1007/s12094-019-02041-x

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