Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma

Michallet, Mauricette; Philip, Thierry; Philip, I; Godinot, Hubert; Sebban, Catherine; Salles, Gilles; Thiébaut, Anne; Biron, Pierre; Lopez, Francis; Mazars, Philippe; Roubi, Nora; Leemhuis, Tom; Hanania, Elie G.; Reading, Christopher L.; Fine, Gilbert; Atkinson, K; Juttner, Chris; Coiffier, Bertrand; Fière, D; Archimbaud, E

doi:10.1016/s0301-472x(00)00169-7

Cited by 102 publications

(65 citation statements)

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“…27,36,37 This would reduce significantly the numbers of vector particles required for cell manipulation, the risk of random mutagenic events that are related to the number of transgene insertions (below), and probably also the costs of the procedure. However, methods required for further enrichment of HSCs, such as isolation of the CD34 ϩ CD38 Ϫ population or their more primitive precursors, 29,[38][39][40] have not yet been established for routine clinical use. High-grade purification of HSCs based on flow cytometry sorting has been shown to be feasible, but concerns remain regarding the risk of contamination, fitness of the sorted cells, selective interference with short-term engraftment, and risks associated with cell expansion.…”

Section: Toxicity Of Cell Manipulationmentioning

confidence: 99%

“…High-grade purification of HSCs based on flow cytometry sorting has been shown to be feasible, but concerns remain regarding the risk of contamination, fitness of the sorted cells, selective interference with short-term engraftment, and risks associated with cell expansion. 39 Although short-term reconstitution may be promoted following cell expansion in vitro, 41 current culture conditions may induce a selective loss of long-term HSCs. 29 Several underlying mechanisms have been identified: commitment to differentiation (loss of pluripotency) or even apoptosis, a cell-cycle-associated loss of engraftment/homing properties, and differential susceptibility to natural killer cell-mediated rejection.…”

Section: Toxicity Of Cell Manipulationmentioning

confidence: 99%

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Side effects of retroviral gene transfer into hematopoietic stem cells

Baum

Düllmann

et al. 2003

Blood

381

241

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Recent conceptual and technical improvements have resulted in clinically meaningful levels of gene transfer into repopulating hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unexpected side effects, based on preclinical and clinical data. To assess the therapeutic potential of genetic interventions in hematopoietic cells, it will be important to derive a classification of side effects, to obtain insights into their underlying mechanisms, and to use rigorous statistical approaches in comparing data. We here review side effects related to target cell manipulation; vector production; transgene insertion and expression; selection procedures for transgenic cells; and immune surveillance. We also address some inherent differences between hematopoiesis in the most commonly used animal model, the laboratory mouse, and in humans. It is our intention to emphasize the need for a critical and hypothesis-driven analysis of "transgene toxicology," in order to improve safety, efficiency, and prognosis for the yet small but expanding group of patients that could benefit from gene therapy. (Blood. 2003;

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Section: Toxicity Of Cell Manipulationmentioning

confidence: 99%

Section: Toxicity Of Cell Manipulationmentioning

confidence: 99%

Side effects of retroviral gene transfer into hematopoietic stem cells

Baum

Düllmann

et al. 2003

Blood

381

241

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“…Additional studies have demonstrated that human HSC also express CD90 (3)(4)(5). Perhaps the best demonstration of HSC function comes from human clinical trials of autologous mobilized peripheral blood in clinical transplantation, where long-term engraftment was provided by transplantation of purified CD34ϩCD90ϩ cells (6)(7)(8). In multiple reports (12)(13)(14), a common phenotype for AML LSC has been identified and found to be negative for expression of lineage markers (Lin-), positive for expression of CD34, and negative for expression of CD38 (9 -11).…”

mentioning

confidence: 99%

Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

Majeti

Becker

Tian

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

253

246

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We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.

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“…Tissues with continuous high turnover, such as the blood and gut, rely heavily on robust stem cell pools (Morrison et al, 1995;Rando, 2006;van der Flier and Clevers, 2009). For example, stem cells present in the bone marrow are the source for continuously replenished erythrocytes, platelets and leukocytes in the blood of humans and rodents (Spangrude et al, 1988;Baum et al, 1992;Osawa et al, 1996;Uchida et al, 1998;Michallet et al, 2000;Shizuru et al, 2005). Intestinal stem cells are the primary source of new epithelial cells in intestinal crypts of humans and mice, and these crypts undergo complete turnover in 4-5 days (van der Flier and Clevers, 2009).…”

mentioning

confidence: 99%