Exonal switch down-regulates the expression of CD5 on blasts of acute T cell leukaemia

A. K. Rai, A. Singh, A. Saxena, T. Seth, V. Raina, D. K. Mitra

Research output: Contribution to journalArticlepeer-review

Abstract

To date, CD5 expression and its role in acute T cell lymphoblastic leukaemia (T-ALL) have not been studied closely. We observed a significant reduction in surface expression of CD5 (sCD5) on leukaemic T cells compared to autologous non-leukaemic T cells. In this study, we have shown the molecular mechanism regulating the expression and function of CD5 on leukaemic T cells. A total of 250 patients suffering from leukaemia and lymphoma were immunophenotyped. Final diagnosis was based on their clinical presentation, morphological data and flow cytometry-based immunophenotyping. Thirty-nine patients were found to be of ALL-T origin. Amplification of early region of E1A and E1B transcripts of CD5 was correlated with the levels of surface and intracellular expression of CD5 protein. Functional studies were performed to show the effect of CD5 blocking on interleukin IL-2 production and survival of leukaemic and non-leukaemic cells. Lack of expression of sCD5 on T-ALL blasts was correlated closely with predominant transcription of exon E1B and significant loss of exon E1A of the CD5 gene, which is associated with surface expression of CD5 on lymphocytes. High expression of E1B also correlates with increased expression of cytoplasmic CD5 (cCD5) among leukaemic T cells. Interestingly, we observed a significant increase in the production of IL-2 by non-leukaemic T cells upon CD5 blocking, leading possibly to their increased survival at 48 h. Our study provides understanding of the regulation of CD5 expression on leukaemic T cells, and may help in understanding the molecular mechanism of CD5 down-regulation.

Original languageEnglish (US)
Pages (from-to)340-350
Number of pages11
JournalClinical and Experimental Immunology
Volume190
Issue number3
DOIs
StatePublished - Dec 2017

Bibliographical note

Funding Information:
All experiments were carried out in the same laboratory. The authors thank all the patients and control subjects who volunteered participation in this study. The authors acknowledge the support from the late Dr Arundhati Pani-grahi, who provided Quantum MESF beads for our experiments. A part of the study was supported by the grant from The Department of Biotechnology, Government of India (GoI). The authors acknowledge the support received at the

Funding Information:
flow cytometry data analysis facility, Centre for Medical Diagnostic and Research (CMDR), MNNIT Allahabad for analysis of data. We are also thankful to Dr J. Philip McCoy, Senior Scientist. Flow Cytometry Core, National Heart, Lung and Blood Institute (NHLBI), National Institute of Health (NIH), Bethesda, MD, USA for his valuable suggestions and editing. The study was carried out as part of routine diagnostic services based on flow cytometer based immunophenotyping at the Cellular Immunology Laboratory, Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences (AIIMS), New Delhi. The authors acknowledge the support received from AIIMS, New Delhi and Department of Biotechnology, Government of India (Ref. no. 6242-P101/RGCB/PMD/ DBT/AMKR/2015).

Keywords

  • CD5
  • T cell
  • acute leukaemia
  • down-regulation
  • immune suppression

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