Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.

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 c...

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Main Authors: Parviz Kokhaei, Mohammad Hojjat-Farsangi, Fariba Mozaffari, Ali Moshfegh, Fatemeh Pak, Ali Rashidy-Pour, Marzia Palma, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5809069?pdf=render
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author Parviz Kokhaei
Mohammad Hojjat-Farsangi
Fariba Mozaffari
Ali Moshfegh
Fatemeh Pak
Ali Rashidy-Pour
Marzia Palma
Lotta Hansson
Anders Österborg
Håkan Mellstedt
author_facet Parviz Kokhaei
Mohammad Hojjat-Farsangi
Fariba Mozaffari
Ali Moshfegh
Fatemeh Pak
Ali Rashidy-Pour
Marzia Palma
Lotta Hansson
Anders Österborg
Håkan Mellstedt
author_sort Parviz Kokhaei
collection DOAJ
description 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.
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spelling doaj.art-fcdf895cba0b43c5a53915ce617f4a252022-12-22T01:55:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01132e019283910.1371/journal.pone.0192839Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.Parviz KokhaeiMohammad Hojjat-FarsangiFariba MozaffariAli MoshfeghFatemeh PakAli Rashidy-PourMarzia PalmaLotta HanssonAnders ÖsterborgHåkan MellstedtCrosstalk 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.http://europepmc.org/articles/PMC5809069?pdf=render
spellingShingle Parviz Kokhaei
Mohammad Hojjat-Farsangi
Fariba Mozaffari
Ali Moshfegh
Fatemeh Pak
Ali Rashidy-Pour
Marzia Palma
Lotta Hansson
Anders Österborg
Håkan Mellstedt
Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
PLoS ONE
title Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
title_full Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
title_fullStr Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
title_full_unstemmed Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
title_short Autologous T cells expressing the oncogenic transcription factor KLF6-SV1 prevent apoptosis of chronic lymphocytic leukemia cells.
title_sort autologous t cells expressing the oncogenic transcription factor klf6 sv1 prevent apoptosis of chronic lymphocytic leukemia cells
url http://europepmc.org/articles/PMC5809069?pdf=render
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