title: The functional duality of HoxB4 in hematopoietic reconstituting cells.
abstract: Transplantation of CD34⁺ hematopoietic reconstituting cells (HRC) is an important treatment modality. The cells needed for clinical hematopoietic reconstitution after myeloablation most commonly derive from bone marrow which have been mobilized into the peripheral blood. The number of CD34⁺ cells in mobilized blood samples is used to indicate the appropriateness of transplantation although it does not evaluate the two necessary functions for successful transplantation: long-term reconstitution mediated by cells with self-renewing proliferation and short-term hematopoietic differentiation mediated by progenitor cells. Using a novel high-resolution immunophenotyping technology on a flow cytometric platform, we have assessed uniformly mobilized CD34⁺ cells for expression levels of 16 molecules previously associated with HRC function and sought correlations of these expression data with functional short-term assays for colony formation that do predict successful transplantation. We found that colony-forming units were significantly correlated with HoxB4 expression, which was explained by the number of CD34⁺ cells in the samples. However, analysis of colony-forming units normalized to the CD34⁺ cell count revealed a significant negative correlation with HoxB4 expression. Thus, increased levels of HoxB4 enhance CD34⁺ cell number via self-renewing expansion but concomitantly depreciate the capacity for short-term differentiation per cell. Our findings demonstrate the translation of experimental findings into a clinical setting and suggest that the expression level of HoxB4 in CD34⁺ cells can be used as a measure of a sample's appropriateness for transplantation.
authors.affiliation: Pathfinder Biotech, 11000 Cedar Avenue, Suite 265, Cleveland, OH 44106, USA. david.kaplan@case.edu
authors.forename: David
authors.initials: D
authors.lastname: Kaplan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kaye
authors.forename: Fangfang
authors.initials: F
authors.lastname: Liu
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Seunghee
authors.initials: S
authors.lastname: Margevicius
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Meyerson
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors