Hematopoietic Stem Cells: Normal<i>Versus</i>Malignant

Carroll, Dustin; Clair, Daret K. St.

doi:10.1089/ars.2017.7326

Cited by 28 publications

(23 citation statements)

References 178 publications

(312 reference statements)

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“…Oxidative metabolism is a key element in both normal and leukemic hematopoiesis. In the last decade, several studies have highlighted the essential role of oxidative metabolism not only in the tight regulation of normal HSCs [ 13 , 17 , 20 ] but also in LSC biology [ 23 , 24 , 48 ]. Thus, low ROS contents have been associated with stemness and quiescence [ 13 , 17 , 20 , 23 ] while intermediate ROS levels were found in more differentiated populations and associated to proliferation and differentiation [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Vignon

Debeissat

Bourgeais

et al. 2020

IJMS

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The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.

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Section: Discussionmentioning

confidence: 99%

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Vignon

Debeissat

Bourgeais

et al. 2020

IJMS

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“…While closing the catalytic cycle, MnPs get reoxidized with either O 2 or oxygen (Eq. [11]), producing H 2 O 2 or O 2 -, respectively. O 2 gets then readily dismuted to H 2 O 2 and O 2 .…”

Section: Redox Properties Of Mn Complexes Control Their Anticancer Efmentioning

confidence: 99%

“…Mn III TE-2-PyP 5 þ þ HA À / ) Mn II TE-2-PyP 4 þ þ HA [10] [11] In aqueous chemistry studies, M40403 is neither able to oxidize Asc nor mimic GPx (10) and has a very low ability to catalyze dismutation of H 2 O 2 (49) ( Table 1). Such data agree well with the lack of anticancer effects in our cellular and animal studies (Figs.…”

Section: Redox Properties Of Mn Complexes Control Their Anticancer Efmentioning

confidence: 99%

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Radiation-Mediated Tumor Growth Inhibition Is Significantly Enhanced with Redox-Active Compounds That Cycle with Ascorbate

Tovmasyan

Bueno-Janice

Jaramillo

et al. 2018

Antioxidants & Redox Signaling

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“…Each day, over 100 billion new blood cells are produced by the human body. These new blood cells, containing more than ten different mature cell types, are derived from a rare population of hematopoietic stem cells (HSCs) throughout a lifetime [1][2][3]. HSCs are the most well-characterized adult stem cell type, and there has been an enormous boost in our understandings of cellular and molecular properties of HSCs, with many studies documenting various pathways involved in the balance between HSC self-renewal and differentiation [3].…”

Section: Introductionmentioning

confidence: 99%

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

Huang

Broxmeyer

2019

Current Opinion in Hematology

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Hematopoietic cell transplantation (HCT) is a life-saving treatment for a variety of hematological and non-hematological disorders. Successful clinical outcomes after transplantation rely on adequate hematopoietic stem cell (HSC) numbers, and the homing and subsequent short-and long-term engraftment of these cells in the bone marrow. Enhancing the homing capability of HSCs has the potential for high impact on improving HCT and patient survival. Recent findings There are a number of ways to enhance HSC engraftment. Neutralizing negative epigenetic regulation by histone deacetylase 5 (HDAC5) increases surface CXCR4 expression and promotes human HSC homing and engraftment in immune deficient (NSG) mice. Short-term treatment of cells with glucocorticoids, pharmacological stabilization of hypoxia inducible factor (HIF)-1α, increasing membrane lipid raft aggregation, and inhibition of Dipeptidyl peptidase 4 (DPP4) facilitates HSC homing and engraftment. Added to these procedures, modulating the mitochondria permeability transition pore (MPTP) to mitigate ambient air induced Extra Physiological Oxygen Stress/Shock (EPHOSS) by hypoxic harvest and processing, or using cyclosporine A during air collection increases functional HSC numbers and improves HSC engraftment. Summary A Better understanding of the regulation of human HSC homing mediated by various signaling pathways will facilitate development of more efficient means to enhance HCT efficacy.

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Hematopoietic Stem Cells: NormalVersusMalignant

Cited by 28 publications

References 178 publications

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Radiation-Mediated Tumor Growth Inhibition Is Significantly Enhanced with Redox-Active Compounds That Cycle with Ascorbate

Progress towards improving homing and engraftment of hematopoietic stem cells for clinical transplantation

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