Molecular Biology Reports

, Volume 46, Issue 1, pp 669–678 | Cite as

PKNOX2 expression and regulation in the bone marrow mesenchymal stem cells of Fanconi anemia patients and healthy donors

  • Ilgin Cagnan
  • Erdal Cosgun
  • Ozlen Konu
  • Duygu Uckan
  • Aysen Gunel-OzcanEmail author
Original Article


HOX and TALE transcription factors are important regulators of development and homeostasis in determining cellular identity. Deregulation of this process may drive cancer progression. The aim of this study was to investigate the expression of these transcription factors in the bone marrow derived mesenchymal stem cells (BM-MSCs) of Fanconi anemia (FA) patients, which is a cancer-predisposing disease. Expression levels of HOX and TALE genes in BM-MSCs were obtained from FA patients and healthy donors by RT-qPCR and highly conserved expression levels were observed between patient and donor cells, except PKNOX2, which is a member of TALE class. PKNOX2 was significantly downregulated in FA cells compared to donors (P < 0.05). PKNOX2 expression levels did not change with diepoxybutane (DEB), a DNA crosslinking agent, in either donor or FA cells except one patient’s with a truncation mutation of FANCA. A difference of PKNOX2 protein level was not obtained between FA patient and donor BM-MSCs by western blot analysis. When human TGF-β1 (rTGF-β1) recombinant protein was provided to the cultures, PKNOX2 as well as TGF-β1 expression increased both in FA and donor BM-MSCs in a dose dependent manner. 5 ng/mL rTGF-β stimulation had more dominant effect on the gene expression of donor BM-MSCs compared to FA cells. Decreased PKNOX2 expression in FA BM-MSCs may provide new insights into the molecular pathophysiology of the disease and TGF-β1 levels of the microenvironment may be the cause of PKNOX2 downregulation.


PKNOX2 HOX genes TALE class TGF-β1 Fanconi anemia Bone marrow mesenchymal stem cells 



This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK; Project No: 110S021 in conjunction with EU COST Action BM0805 designated as ‘HOX and TALE transcription factors in Development and Disease’ and TUBITAK Project No: 214Z033). The data in this study is a part of Ilgin Cagnan’s Ph.D. thesis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11033_2018_4522_MOESM1_ESM.pdf (7.6 mb)
Supplementary material 1 (PDF 7823 KB)
11033_2018_4522_MOESM2_ESM.pdf (114 kb)
Supplementary material 2 (PDF 114 KB)
11033_2018_4522_MOESM3_ESM.pdf (188 kb)
Supplementary material 3 (PDF 188 KB)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Stem Cell Sciences, Graduate School of Health Sciences, Center for Stem Cell Research and DevelopmentHacettepe UniversityAnkaraTurkey
  2. 2.Department of Biostatistics, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  3. 3.Department of Molecular Biology and GeneticsBilkent UniversityAnkaraTurkey
  4. 4.Department of Pediatrics, Division of Bone Marrow Transplantation Unit, Faculty of MedicineHacettepe UniversityAnkaraTurkey
  5. 5.Blood Bank, Burhan Nalbantoglu State HospitalNicosiaNorth Cyprus
  6. 6.Microsoft ResearchRedmondUSA

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