title: Deregulated expression of Kruppel-like factors in acute myeloid leukemia.
abstract: 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.
authors.affiliation: Department of Clinicial Research, Experimental Oncology and Hematology, University of Bern, and Department of Hematology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Magali
authors.initials: M
authors.lastname: Humbert
authors.forename: Veronika
authors.initials: V
authors.lastname: Halter
authors.forename: Deborah
authors.initials: D
authors.lastname: Shan
authors.forename: Judith
authors.initials: J
authors.lastname: Laedrach
authors.forename: Elisabeth Oppliger
authors.initials: EO
authors.lastname: Leibundgut
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: Andreas
authors.initials: A
authors.lastname: Tobler
authors.forename: Martin F
authors.initials: MF
authors.lastname: Fey
authors.forename: Mario P
authors.initials: MP
authors.lastname: Tschan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C096161:KLF2 protein, human; C501168:KLF3 protein, human; C492214:KLF5 protein, human; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014212:Tretinoin