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

PLoS One. 2018 Feb 12;13(2):e0192839. doi: 10.1371/journal.pone.0192839. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Female
  • Gene Expression
  • Humans
  • Kruppel-Like Factor 6 / antagonists & inhibitors
  • Kruppel-Like Factor 6 / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / pathology
  • Oncogenes
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • RNA, Small Interfering / genetics
  • T-Lymphocytes / metabolism*
  • Transfection
  • Tumor Microenvironment / genetics


  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering

Grants and funding

This work was supported by The Swedish Cancer Society,, Award Number: 160534, Recipient: AÖ; The Cancer Society in Stockholm,, Award Number: 151313, Recipient: AÖ; The King Gustav Vth Jubilee Fund,, Award Number: 144193, Recipient: AÖ; AFA Försäkring,, Award Number: 130054, Recipient: AÖ; The Cancer and Allergy Foundation,, Award Number: 150420, 150122, 64, Recipient: HM; The Stockholm County Council,, Award Number: 20120051, 20150070, Recipient: AÖ; and The Karolinska Institute Foundation,, Award Number: None, Recipient: LH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.