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Myc and AP-1 expression in T cells and T-cell activation in patients after hematopoietic stem cell transplantation

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Abstract

Regeneration of the immune system after hematopoietic stem cell transplantation (HSCT) is a slow process. We attempted to identify problems in the recovery of the immune system by examining expressions of early event cell cycle proteins Myc, Jun, and Fos, as well as DNA binding of Myc, activating protein 1 (AP-1), and CD4 cell activation values, in phytohemagglutinin-activated T lymphocytes taken from patients after HSCT. HSCT patients showed lower protein expression levels of Myc and Jun, as well as Myc and AP-1 DNA-binding levels, as compared to healthy controls. C-Jun was lower in long-term survivors of HSCT than short-term survivors. Adenosine triphosphate (ATP) values in CD4 cells were also lower in HSCT patients than healthy controls, but showed a time-dependent increase post-transplant. Non-surviving patients showed lower levels of both Fos protein and ATP as compared to surviving patients and a negative correlation between Fos values and lymphocyte percentage that was not present in surviving patients. There was a strong positive correlation between Fos values and lymphocyte percentage and between AP-1 values and white blood count, in patients without graft-versus-host disease (GVHD), that did not exist in patients who suffered from GVHD. Patients 2 years post-HSCT showed a positive correlation between AP-1 and Myc DNA-binding protein values, similar to those values found in healthy controls. Our study identified significant factors that account for the delay in immune reconstitution after transplant; this knowledge may improve the management of post-HSCT patients.

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Acknowledgments

The authors of this paper wish to thank the staff at the bone marrow transplant outpatient clinic for their assistance in the collection of blood samples and clinical follow-up data and the staff members at our laboratory. We also thank Aviva Yoselis of Israel Health Consulting for her editorial assistance.

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Authors and Affiliations

  1. Faculty of Medicine, The Institute of Medical Research, Hebrew University of Jerusalem, Jerusalem, Israel

    Shivtia Trop-Steinberg

  2. Department of Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Hadassah Medical Organization, Kiryat Hadassah, P.O.B. 12000, 91120, Jerusalem, Israel

    Shivtia Trop-Steinberg, Yehudith Azar, Rachel Bringer & Reuven Or

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  1. Shivtia Trop-Steinberg
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  2. Yehudith Azar
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Correspondence to Reuven Or.

Appendix: Evaluation of CD3+ T-cell purity

Appendix: Evaluation of CD3+ T-cell purity

Flow cytometry analysis of the enriched cells after the RosetteSep cocktail showed a CD3+ T-cell purity of 95–97 %.

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Trop-Steinberg, S., Azar, Y., Bringer, R. et al. Myc and AP-1 expression in T cells and T-cell activation in patients after hematopoietic stem cell transplantation. Clin Exp Med 15, 189–203 (2015). https://doi.org/10.1007/s10238-014-0285-6

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  • DOI: https://doi.org/10.1007/s10238-014-0285-6

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