title: DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia (AML).
abstract: DEK is important in regulating cellular processes including proliferation, differentiation and maintenance of stem cell phenotype. The translocation t(6;9) in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor prognosis and a higher risk of relapse. The over-expression of DEK in AML has been reported, but different studies have shown diminished levels in pediatric and promyelocytic leukemias. This study has characterized DEK expression, in silico, using a large multi-center cohort of leukemic and normal control cases. Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM). Studying specific subtypes of AML confirmed either no significant change or a significant reduction in DEK expression compared to NBM. Importantly, the similarity of DEK expression between AML and NBM was confirmed using immunohistochemistry analysis of tissue mircorarrays. In addition, stratification of AML patients based on median DEK expression levels indicated that DEK showed no effect on the overall survival of patients. DEK expression during normal hematopoiesis did reveal a relationship with specific cell types implicating a distinct function during myeloid differentiation. Whilst DEK may play a potential role in hematopoiesis, it remains to be established whether it is important for leukemagenesis, except when involved in the t(6;9) translocation.
authors.affiliation: Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, United Kingdom. Electronic address: glogan05@qub.ac.uk.
authors.forename: Gemma E
authors.initials: GE
authors.lastname: Logan
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA. Electronic address: morvak@med.umich.edu.
authors.forename: Nirit
authors.initials: N
authors.lastname: Mor-Vaknin
authors.affiliation: Institute of Pathology, Medical School, RWTH Aachen University, Aachen, Germany. Electronic address: tbraunschweig@ukaachen.de.
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.affiliation: Clinic for Oncology, Hematology and Stem Cell Transplantation, Medical School, RWTH Aachen University, Aachen, Germany. Electronic address: EJost@ukaachen.de.
authors.forename: Edgar
authors.initials: E
authors.lastname: Jost
authors.affiliation: Clinic for Oncology, Hematology and Stem Cell Transplantation, Medical School, RWTH Aachen University, Aachen, Germany. Electronic address: pia.verena.schmidt@gmx.de.
authors.forename: Pia Verena
authors.initials: PV
authors.lastname: Schmidt
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA. Electronic address: dmarkov@med.umich.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
authors.affiliation: Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, United Kingdom. Electronic address: k.mills@qub.ac.uk.
authors.forename: Ken I
authors.initials: KI
authors.lastname: Mills
authors.affiliation: Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Aachen, Germany. Electronic address: kappesferdinand1@gmail.com.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kappes
authors.affiliation: Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, United Kingdom; Haematology Department, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, United Kingdom. Electronic address: m.percy@qub.ac.uk.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Percy
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D030541:Databases, Genetic; D018572:Disease-Free Survival; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015337:Multicenter Studies as Topic; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D015996:Survival Rate; D014178:Translocation, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C519564:DEK protein, mouse; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins
keywords: Acute Myeloid Leukemia; DEK; Hematopoiesis; Leukemagenesis; Translocation t(6;9)