The hypoxia signalling pathway in haematological malignancies

Irigoyen, Marta; García‐Ruiz, Juan Carlos; Berra, Edurne

doi:10.18632/oncotarget.15981

Cited by 33 publications

(27 citation statements)

References 164 publications

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“…We have further demonstrated that residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy ( 59 ). Altogether these data support the pivotal role of hypoxia signaling in leukemias ( 60 ). Albeit our conclusions in the current study are limited to demonstrating the utility of complex I inhibition in alleviating the leukemic BM hypoxia, this finding may ultimately lead to important translational implications to be tested in subsequent studies.…”

Section: Discussionsupporting

confidence: 75%

Inhibition of Oxidative Phosphorylation Reverses Bone Marrow Hypoxia Visualized in Imageable Syngeneic B-ALL Mouse Model

et al. 2020

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Section: Discussionsupporting

confidence: 75%

Inhibition of Oxidative Phosphorylation Reverses Bone Marrow Hypoxia Visualized in Imageable Syngeneic B-ALL Mouse Model

et al. 2020

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“…Hypoxia is also present in bone marrow hematopoietic niches where B lineage cells reside [15]. Therefore, in this study, we analyzed the effects of hypoxia on CD19 CAR-T cells [16,17] and B cell maturation antigen (BCMA) CAR-T cells in vitro [18].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Selectively Impairs CAR-T Cells In Vitro

Berahovich

Liu

Zhou

et al. 2019

Cancers

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Hypoxia is a major characteristic of the solid tumor microenvironment. To understand how chimeric antigen receptor-T cells (CAR-T cells) function in hypoxic conditions, we characterized CD19-specific and BCMA-specific human CAR-T cells generated in atmospheric (18% oxygen) and hypoxic (1% oxygen) culture for expansion, differentiation status, and CD4:CD8 ratio. CAR-T cells expanded to a much lower extent in 1% oxygen than in 18% oxygen. Hypoxic CAR-T cells also had a less differentiated phenotype and a higher CD4:CD8 ratio than atmospheric CAR-T cells. CAR-T cells were then added to antigen-positive and antigen-negative tumor cell lines at the same or lower oxygen level and characterized for cytotoxicity, cytokine and granzyme B secretion, and PD-1 upregulation. Atmospheric and hypoxic CAR-T cells exhibited comparable cytolytic activity and PD-1 upregulation; however, cytokine production and granzyme B release were greatly decreased in 1% oxygen, even when the CAR-T cells were generated in atmospheric culture. Together, these data show that at solid tumor oxygen levels, CAR-T cells are impaired in expansion, differentiation and cytokine production. These effects may contribute to the inability of CAR-T cells to eradicate solid tumors seen in many patients.

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“…Foam-based 3D culture similar to fiber scaffolds [16] increased the resistance of the leukaemia cell lines to inhibitory effects of imatinib and to the maintenance of AML cells [29,30] and also selects bortezomib-resistant CML stem cells [31]. It has been shown that 3D-cultures are better than 2D-cultures in simulating important tumor characteristics in vivo such as hypoxia and resulting drug resistant phenotype [32].…”

Section: Discussionmentioning

confidence: 99%

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

Karimpoor

Yebra-Fernandez

Parhizkar

et al. 2018

J. R. Soc. Interface.

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The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells.

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The hypoxia signalling pathway in haematological malignancies

Cited by 33 publications

References 164 publications

Inhibition of Oxidative Phosphorylation Reverses Bone Marrow Hypoxia Visualized in Imageable Syngeneic B-ALL Mouse Model

Inhibition of Oxidative Phosphorylation Reverses Bone Marrow Hypoxia Visualized in Imageable Syngeneic B-ALL Mouse Model

Hypoxia Selectively Impairs CAR-T Cells In Vitro

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

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