GAMMARETROVIRUS-MEDICATED TRANSFER OF P21SNFT CAUSES MALIGNANT TRANSFORMATION OF MATURE T CELLS
Ashok Kumar1, Saira Baloch2, Lata1, Dr. Syed Muhammad Irfan3, Abdul Malik Tareen4, Manzoor Ali Abro5
1Department of Pathology, Isra University, Hyderabad, Pakistan
2Medical Research Centre, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
3Liaquat National Hospital & Medical College, Karachi, Pakistan
4Department of Microbiology, University of Baluchistan, Quetta, Pakistan
5 Sindh Agriculture University, Tandojam, Pakistan
Background. The role of p21SNFT (21-kDa small nuclear factor isolated from T cells) gene was not clear if it exerted its oncogenic effects to cause lymphoma. Previously, it was shown that p21SNFT is up-regulated in primary Hodgkins’ lymphoma and classical Hodgkins’ lymphoma cell lines. Contrary to that, it was also shown that p21SNFT causes decreased production of T cell growth factor IL-2 (interleukin 2) in Jurkat T cell line, which is disadvantageous for the growth of T cells.
Objective. To investigate if p21SNFT gene exerts its oncogenic effects to cause lymphoma.
Design. p21SNFT was cloned into gammaretroviral vector and transduced into murine haematopoietic stem/progenitor cells (HCSs/HPCs), mature polyclonal T cells (both isolated from wild type C57BL/6 Ly 5.1 mice) and mature monoclonal OT-1 T cells, isolated from T cell receptor (TCR) transgenic mice (OT-1). Subsequently, the cells were transplanted into Rag-1 deficient mice.
Results. 6 out of 7 mice transplanted with p21SNFT-transduced monoclonal OT-1 T cells developed lymphoma, while only 1 out of 7 mice transplanted with p21SNFT-transduced polyclonal T cells developed lymphoma after characteristic latency periods. None of the mice transplanted with p21SNFT transduced HCSs/HPCs, or from the control groups (transplanted with control vector transduced HSCs/polyclonal T/monoclonal T cells) developed any malignancy.
Conclusion. Results of the present study show that p21SNFT is an oncogene, which causes malignant transformation of mature T lymphocytes.