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  • 1
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    Medicine. The blood stem cell Holy Grail? (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sauvageau, Guy -- Humphries, R Keith -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1291-2. doi: 10.1126/science.1195173.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer, University of Montreal, Montreal, QC H3C 3J7, Canada. guy.sauvageau@umontreal.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829472" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD34/analysis ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Fetal Blood/cytology ; *Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology/*drug effects/physiology ; Humans ; Mice ; Purines/chemistry/metabolism/*pharmacology ; Receptors, Aryl Hydrocarbon/*antagonists & inhibitors/metabolism ; Small Molecule Libraries ; Species Specificity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Cord blood expansion. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-09-23
    Description: The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372335/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372335/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fares, Iman -- Chagraoui, Jalila -- Gareau, Yves -- Gingras, Stephane -- Ruel, Rejean -- Mayotte, Nadine -- Csaszar, Elizabeth -- Knapp, David J H F -- Miller, Paul -- Ngom, Mor -- Imren, Suzan -- Roy, Denis-Claude -- Watts, Kori L -- Kiem, Hans-Peter -- Herrington, Robert -- Iscove, Norman N -- Humphries, R Keith -- Eaves, Connie J -- Cohen, Sandra -- Marinier, Anne -- Zandstra, Peter W -- Sauvageau, Guy -- HL84345/HL/NHLBI NIH HHS/ -- R01 HL084345/HL/NHLBI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Sep 19;345(6203):1509-12. doi: 10.1126/science.1256337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada. ; Medicinal Chemistry, IRIC, University of Montreal, Montreal, QC, Canada. ; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada. ; Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada. ; Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada. ; Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. ; Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA. Department of Medicine and Pathology, University of Washington, Seattle, WA, USA. ; Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. ; Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. Department of Immunology, University of Toronto, Toronto, ON, Canada. ; Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC, Canada. Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, QC, Canada. Department of Medicine, Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada. guy.sauvageau@umontreal.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25237102" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; Fetal Blood/cytology/*drug effects/physiology ; Genetic Therapy/methods ; Hematopoiesis/*drug effects/physiology ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/*drug effects/physiology ; Humans ; Immunocompromised Host ; Indoles/chemistry/*pharmacology ; Mice ; Pyrimidines/chemistry/*pharmacology ; Receptors, Aryl Hydrocarbon/*antagonists & inhibitors ; Regeneration/*drug effects ; Small Molecule Libraries/chemistry/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. (1994)
    National Academy of Sciences
    Details
    Publication Date: 1994-12-06
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 4
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    An anticlastogenic function for the Polycomb Group gene Bmi1 (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-03-14
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Ribosomal proteins regulate ESC fate [Genetics] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-02-18
    Description: In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity for three RP genes (Rps5, Rps14, or Rps28), distinguished by the proximity of their corresponding...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    An anticlastogenic function for the Polycomb Group gene Bmi1 [Cell Biology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-03-30
    Description: BMI1 is a key component of multiprotein Polycomb repression complex 1 (PRC1), and its disruption in mice induces severe aplastic anemia by early adulthood. The contributing mechanisms responsible for this phenotype remain elusive. Here we show that transformed human cell lines as well as primitive hematopoietic cells exhibit a high frequency of spontaneous chromosome breaks upon BMI1 depletion and are hypersensitive to genotoxic agents. Consistent with these observations, we found that BMI1 is recruited rapidly to DNA damage foci where it blocks transcriptional elongation. We also show that BMI1 contributes to homologous recombination DNA repair and is required for checkpoint recovery. Taken together, our results suggest that BMI1 is critical for the maintenance of chromosome integrity in both normal and transformed cells.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    In vitro stem cell expansion: Stepping closer towards self-renewal (2006)
    Springer Nature
    Details
    Publication Date: 2006-06-01
    Print ISSN: 0969-7128
    Electronic ISSN: 1476-5462
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 8
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    Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro (1996)
    American Society of Hematology
    Details
    Publication Date: 1996-04-01
    Description: Little is known about the molecular mechanisms controlling primitive hematopoietic stem cells, especially during embryogenesis. Homeobox genes encode a family of transcription factors that have gained increasing attention as master regulators of developmental processes and recently have been implicated in the differentiation and proliferation of hematopoietic cells. Several Hox homeobox genes are now known to be differentially expressed in various subpopulations of human hematopoietic cells and one such gene, HOXB4, has recently been shown to positively determine the proliferative potential of primitive murine bone marrow cells, including cells with long-term repopulating ability. To determine if this gene might influence hematopoiesis at the earliest stages of development, embryonic stem (ES) cells were genetically modified by retroviral gene transfer to overexpress HOXB4 and the effect on their in vitro differentiation was examined. HOXB4 overexpression significantly increased the number of progenitors of mixed erythroid/myeloid colonies and definitive, but not primitive, erythroid colonies derived from embryoid bodies (EBs) at various stages after induction of differentiation. There appeared to be no significant effect on the generation of granulocytic or monocytic progenitors, nor on the efficiency of EB formation or growth rate. Analysis of mRNA from EBs derived from HOXB4-transduced ES cells on different days of primary differentiation showed a significant increase in adult beta-globin expression, with no detectable effect on GATA-1 or embryonic globin (beta H-1). Thus, HOXB4 enhances the erythropoietic, and possibly more primitive, hematopoietic differentiative potential of ES cells. These results provide new evidence implicating Hox genes in the control of very early stages in the development of the hematopoietic system and highlight the utility of the ES model for gaining insights into the molecular genetic regulation of differentiation and proliferation events.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 9
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    Autologous Bone Marrow Transplant after Failed Peripheral Blood Stem Cell Mobilization Does Not Adversely Affect Engraftment or Transplant Related Toxicity. (2005)
    American Society of Hematology
    Details
    Publication Date: 2005-11-16
    Description: Introduction: Chemotherapy and G-CSF are widely used to collect adequate numbers of peripheral blood stem cells (PBSC) prior to autologous transplant. However, 10–30% of patients (pts) will not mobilize adequately. Alternatives include use of stem cell factor (SCF) and bone marrow (BM) harvest. Limited information is available on the hematopoietic reconstitution and clinical outcome of intensively treated pts who fail to mobilize sufficient numbers of PBSC and receive BM grafts. We sought to determine whether BM is an acceptable source of stem cells in these pts. Methods: We conducted a retrospective analysis of toxicity, engraftment parameters, transfusion requirements and outcome in pts who failed mobilization and underwent unprimed BM harvest at our institution. Results: Between 02/97 and 07/05, 47 heavily pre-treated pts (male/female 22/27; median age 49, range 22–66) who failed mobilization underwent an autologous BM transplant. Diagnoses included non-Hodgkin’s lymphoma (n=37: 17 low grade and 20 intermediate grade), Hodgkin’s lymphoma (n=6), and multiple myeloma (n=4). Median number of chemotherapy cycles prior to harvest was 11 (range 5–20); 17 pts (36%) had previously received radiotherapy. 42 pts had 1 mobilization attempt and 5 pts had 2 attempts. Mobilization regimens included chemotherapy(C) + G-CSF (n=27), C + G-CSF + SCF (n=20), G-CSF + SCF (n=4) and C + GM-CSF (n=1). G-CSF was given at a minimum dose of 10μg/kg/day. Pts were defined as poor mobilizers if the peak value of CD34+ cells during mobilization was lower than 10 cells/μL (n=33) or in the case of stem cell collection, if less than 1 x 106 CD34+ cells/kg were obtained (n=14). Conditioning regimens included: BEAC (n=38), Cy-TBI (n=5), high dose Melphalan (n=3), and BEAM (n=1). Infused median numbers of nucleated BM cells, CFU-GM and CD34+ cells per kilogram were 3.5×108 (range 1.0–21.6), 7.33×104 (range 0.3–52.7), and 1.1×106 (range 0.3–2.3), respectively. 34 pts received G-CSF during their hospitalization (median 12 days; range 2–38). Following transplant, median times to achieve an ANC 〉 0.5×109/L and platelet count 〉20×109/L were 19 (range 10–42) and 24 days (range 9–233), respectively; median time to RBC transfusion independence was 33 days (range 1–425). Median time to hospital discharge was 25 days (range 14–64). With a median follow-up of 36 months (range 1–97), Kaplan-Meier estimates of overall and disease-free survival at 3 years are 67% and 44%, respectively. The Kaplan-Meier estimates of transfusion independence for platelets and RBC at 3 months are 86% and 84%, and at 1 year 97% and 95%, respectively. 2 pts (4.3%) experienced procedure related deaths prior to day +100, one of cardiac insufficiency on day +3 and one of septic shock on day +90. Cumulative incidences of non relapse mortality at 1, 3 and 5 years were 4.3%, 10.6% and 14.9%, respectively. The incidence of post transplant MDS/AML was 10.6%. Conclusion: Autologous transplant with unprimed BM graft after failed PBSC mobilization does not adversely affect engraftment or transplant related toxicity significantly. Thus, hard to mobilize patients should not be excluded from a potentially curative treatment.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    Hox Homeodomain Proteins Exhibit Selective Complex Stabilities with Pbx and DNA (1996)
    Oxford University Press
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    Publication Date: 1996-01-01
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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