title: Inability of HOXB4 to enhance self-renewal of malignant B cells: favorable profile for the expansion of autologous hematopoietic stem cells.
abstract: Leukemic stem cells share self-renewal properties and slow proliferation with hematopoietic stem cells. Based on expression signatures, it has been suggested that these cells use the same molecular pathways for these processes. However, it is not clear whether leukemic stem cells also respond to factors known to enhance the self-renewal activity of hematopoietic stem cells. The transcription factor homeobox B4 (HOXB4) is known to induce expansion of mouse hematopoietic stem cells. The recombinant TAT-HOXB4 protein also expands human CD34+ cells. In this study we investigated whether overexpression of HOXB4 could increase leukemic initiating cell numbers, an issue that is crucial to its clinical usage. A transgenic mouse model for E2A-PBX1 induced pre-B acute lymphoblastic leukemia was used in combination with HOXB4 transgenic mice to test oncogenic interactions between HOXB4 and E2A-PBX1. The frequency of leukemic initiating cells retrovirally overexpressing HOXB4 was measured by transplantation at limiting dilution and evaluation of leukemia development in recipient mice. Moreover, human B cell lines were evaluated for their colony forming cell potential upon exposure to TAT-HOXB4 protein. Our data with the mouse models show that HOXB4 neither accelerates the generation of E2A-PBX1 B cell leukemia nor expands the number of leukemia initiating cells. Additionally, the growth or colony forming cell proportions of human B cell lines was not changed by HOXB4, suggesting that human B leukemic initiating cells are not affected by HOXB4.
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: Marilaine
authors: M
authors: Fournier
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: Isabelle
authors: I
authors: Savoie-Rondeau
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: Fannie
authors: F
authors: Larochelle
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: Mona
authors: M
authors: Hassawi
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
authors: Elena A
authors: EA
authors: Shestakova
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Départment de Médecine, Université de Montréal, Montréal, QC, Canada.
authors: Denis Claude
authors: DC
authors: Roy
authors: Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Départment de Médecine, Université de Montréal, Montréal, QC, Canada. Electronic address: janettabijl@yahoo.ca.
authors: Janetta J
authors: JJ
authors: Bijl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D015153:Blotting, Western; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors