Semnan University of Medical Sciences

Research and Technology Vice Chancellor

Gibson, Spencer B. and Kokhaei, Parviz and Hojjat-Farsangi, Mohammad and Mozaffari, Fariba and Moshfegh, Ali and Pak, Fatemeh and Rashidy-Pour, Ali and Palma, Marzia and Hansson, Lotta and Österborg, Anders and Mellstedt, Håkan (2018) Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells. PLOS ONE, 13 (2). e0192839. ISSN 1932-6203

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Abstract

Crosstalk between leukemic cells and the tumor microenvironment is of importance in chronic lymphocytic leukemia (CLL). T cells seem to sustain the survival of CLL cells by various mechanisms. The Krüppel-like family of transcription factors (KLFs) are identified as regulators of proliferation and cell death. In the present study, we analyzed the expression of the wild type (WT) gene KLF6 and the oncogenic splice variant 1 (KLF6-SV1) at the mRNA level in subsets of T cells from CLL patients (n = 29), multiple myeloma patients (n = 6) and normal donors (n = 10). RNA Silencing was used for wtKLF6 and KLF6-SV1. Tumor cell apoptosis was measured. A significant overexpression of wtKLF6 and KLF6-SV1 in T cells of CLL patients compared to normal donors and myeloma patients was noted (p<0.002). Western blot showed that both wtKLF6 and KLF6-SV1 were expressed in purified T cells from CLL patients. KLF6-SV1 siRNA transfection induced a significant down-regulation of KLF6-SV1 in CLL T cells, which lost the capability to sustain the growth of leukemic cells. However, no such a significant effect was seen after wtKLF6 transfection of the autologous T cells. The results suggest that KLF6-SV1 may play a role in the regulation of survival CLL cells.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medical Sciences > School of Medicine
Depositing User: Mr Vahab Moshtaghi
Date Deposited: 05 May 2018 07:55
Last Modified: 23 May 2018 09:57
URI: http://eprints.semums.ac.ir/id/eprint/1384

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