title: Cord Blood-Derived Quiescent CD34+ Cells Are More Transcriptionally Matched to AML Blasts Than Cytokine-Induced Normal Human Hematopoietic CD34+ Cells.
abstract: Acute myeloid leukemia (AML) is characterized by developmental arrest, which is thought to arise from transcriptional dysregulation of myeloid development programs. Hematopoietic stem and progenitor cells (HSPCs) isolated from human blood are frequently used as a normal comparator in AML studies. Previous studies have reported changes in the transcriptional program of genes involved in proliferation, differentiation, apoptosis, and homing when HSPCs were expanded ex vivo. The intrinsic functional differences between quiescent and dividing CD34+ HSPCs prompted us to determine whether fresh or cytokine-induced cord blood-derived CD34+ HSPCs are a more appropriate normal control compared to AML blasts. Based on principal component analysis and gene expression profiling we demonstrate that CD34+ HSPCs that do not undergo ex vivo expansion are transcriptionally similar to minimally differentiated AML blasts. This was confirmed by comparing the cell cycle status of the AML blasts and the HSPCs. We suggest that freshly isolated CD34+ HSPCs that do not undergo ex vivo expansion would serve as a better control to identify novel transcriptional targets in the AML blast population.
authors.affiliation: Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.|Cardiff Cancer Genomics Biomedical Research Unit, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Chinmay
authors.initials: C
authors.lastname: Munje
authors.affiliation: Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.affiliation: Faculty of Medical and Human Sciences, Faculty Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Whetton
authors.affiliation: Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.affiliation: Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Darley
authors.affiliation: Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Tonks
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005312:Fetal Blood / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D018952:Antigens, CD34; D016207:Cytokines