Deregulated expression of Kruppel-like factors in acute myeloid leukemia

Humbert, Magali; Halter, Veronika; Shan, Deborah; Laedrach, Judith; Leibundgut, Elisabeth Oppliger; Baerlocher, Gabriela M; Tobler, Andreas; Fey, Martin F; Tschan, Mario P (2011). Deregulated expression of Kruppel-like factors in acute myeloid leukemia. Leukemia research, 35(7), pp. 909-13. Amsterdam: Elsevier 10.1016/j.leukres.2011.03.010

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The known participation of Kruppel-like transcription factors (KLF) in cellular differentiation prompted us to investigate their expression in acute myeloid leukemia (AML) blast cells that are typically blocked in their differentiation. We determined the expression patterns of KLFs with a putative role in myeloid differentiation in a large cohort of primary AML patient samples, CD34+ progenitor cells and granulocytes from healthy donors. We found that KLF2, KLF3, KLF5 and KLF6 are significantly lower expressed in AML blast and CD34+ progenitor cells as compared to normal granulocytes. Moreover, we found markedly increased KLF levels in acute promyelocytic leukemia patients who received oral ATRA. Accordingly, we observed a strong induction of KLF5/6 upon ATRA-treatment in NB4 and HT93 APL but not in ATRA-resistant NB4-R cells. Lastly, knocking down KLF5 or KLF6 in NB4 cells significantly attenuated neutrophil differentiation. In conclusion, we found a significant repression of KLF transcription factors in primary AML samples as compared to mature neutrophils and further show that KLF5 and KLF6 are functionally involved in neutrophil differentiation of APL cells.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
UniBE Contributor:	Oppliger Leibundgut, Elisabeth, Baerlocher, Gabriela M., Fey, Martin, Tschan, Mario Paul
ISSN:	0145-2126
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:18
Last Modified:	05 Dec 2022 14:05
Publisher DOI:	10.1016/j.leukres.2011.03.010
PubMed ID:	21470678
Web of Science ID:	000291470800031
URI:	https://boris.unibe.ch/id/eprint/5857 (FactScience: 210711)