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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

  • J.-R. Romero-Macías
  • R. Pascual-Serra
  • O. Roche
  • F. Ruiz-Marcos
  • A. Serrano-Martínez
  • P. González-Aguado
  • B. Belandia
  • M.-J. Ruiz-Hidalgo
  • R. Sánchez-PrietoEmail author
Brief Research Article
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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.

Keywords

Autophagy Chronic lymphocytic leukemia p62 LC3 Autophagic flux 

Abbreviations

CLL-B

Chronic lymphocytic leukemia of B cells

WB

Western blot

PBMCs

Peripheral blood mononuclear cells

AP

Autophagy

Notes

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).

Compliance with ethical standards

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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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  • J.-R. Romero-Macías
    • 1
    • 2
  • R. Pascual-Serra
    • 2
  • O. Roche
    • 2
    • 3
    • 4
  • F. Ruiz-Marcos
    • 1
  • A. Serrano-Martínez
    • 1
  • P. González-Aguado
    • 1
  • B. Belandia
    • 5
    • 6
  • M.-J. Ruiz-Hidalgo
    • 2
    • 3
    • 7
  • R. Sánchez-Prieto
    • 4
    • 5
    • 6
    Email author
  1. 1.Servicio de HematologíaComplejo Hospitalario Universitario de AlbaceteAlbaceteSpain
  2. 2.Laboratorio de Oncología Molecular, Unidad de Medicina Molecular, Centro Regional de Investigaciones BiomédicasUniversidad de Castilla-La ManchaAlbaceteSpain
  3. 3.Unidad Asociada de Biomedicina CSIC-UCLMAlbaceteSpain
  4. 4.Departamento de Ciencias Médicas, Facultad de MedicinaUniversidad de Castilla-La ManchaAlbaceteSpain
  5. 5.Lab. 1.5.2, Departamento de Biología del CáncerInstituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM)MadridSpain
  6. 6.Unidad Asociada de Biomedicina CSIC-UCLMMadridSpain
  7. 7.Área de Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad de Castilla-La ManchaAlbaceteSpain

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