Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts

Durual, Stéphane; Rideau, Alexandra; Ruault-Jungblut, Sylvie; Cossali, Dominique Anouck; Beris, Photis; Piguet, Vincent; Matthes, Thomas

doi:10.1038/sj.leu.2404645

Cited by 26 publications

(20 citation statements)

References 30 publications

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“…These data are novel in that previous studies have reported the restoration of PU.1 to promote differentiation induction by ATRA and did not address its role in RXR-mediated myeloid differentiation. 8,38 Coactivation of LXR/RXR complexes (and not activation of PPARg/RXR or suppression of RORa/g) induced a potent differentiation response in multiple AML cell lines and primary AML cells (Figures 5-7). Of note, studies demonstrate PPARg responses with rexinoids had pretreated cells with PMA, which was later found to increase PPARg levels.…”

Section: Discussionmentioning

confidence: 99%

Induced differentiation of acute myeloid leukemia cells by activation of retinoid X and liver X receptors

et al. 2013

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Use of all-trans retinoic acid (ATRA) as a differentiation agent has been limited to acute promyelocytic leukemia (APL) as non-APL leukemias are insensitive to ATRA. We recently demonstrated that the rexinoid, bexarotene, induces differentiation and therapeutic responses in patients with refractory AML. Rexinoids bind and activate retinoid X receptors (RXRs); however, rexinoids alone are incapable of activating retinoic acid receptor (RAR)/RXR complexes, suggesting that myeloid differentiation can occur independent of RAR. In this study, we demonstrate that rexinoid differentiation of AML cells is RAR independent and requires the expression of PU.1. Because of the promiscuousness of RXR with other nuclear receptors, myeloid differentiation by bexarotene with other nuclear receptor ligands was explored. Bexarotene cooperated with ATRA to enhance differentiation in some AML cell lines; however, the combination of bexarotene with the PPARγ agonist rosiglitazone did not. In contrast, bexarotene combined with liver X receptor (LXR) agonists, T0901317 or GW3965, induced potent differentiation and cytotoxicity in AML cell lines and primary human AML cells, but not in normal progenitor cells. These results suggest that RXR/LXR-regulated gene expression in normal cells is deregulated in AML cells and identifies a potential role for these agonists in differentiation therapy of non-APLs.

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Section: Discussionmentioning

confidence: 99%

Induced differentiation of acute myeloid leukemia cells by activation of retinoid X and liver X receptors

et al. 2013

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“…In the past, strategies to rescue PU.1 expression in AML cells have been explored. Overexpression of PU.1 is sufficient to trigger neutrophil differentiation in acute promyelocytic leukemia (APL) and leads to differentiation and apoptosis of various primary AML samples (5,21). However, elevation of PU.1 levels or activity is difficult to achieve pharmacologically.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of the transcription factor PU.1 in leukemia

Antony-Debré

Paul

Leite

et al. 2017

Journal of Clinical Investigation

100

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“…Although a CHO-derived cell line was employed for the studies here, it is conceivable that GFP-expressing primary cells could also be used to screen potential scaffold materials. Current DNA delivery methods like nucleofection (Hamm et al 2002) or viral gene delivery (Durual et al 2007) allow the efficient transfection of different cell types, particularly primary cells.…”

Section: Discussionmentioning

confidence: 99%

Suspension-adapted Chinese hamster ovary-derived cells expressing green fluorescent protein as a screening tool for biomaterials

et al. 2009

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Synthetic biomaterials play an important role in regenerative medicine. To be effective they must support cell attachment and proliferation in addition to being non-toxic and non-immunogenic. We used a suspension-adapted Chinese hamster ovary-derived cell line expressing green fluorescent protein (GFP) to assess cell attachment and growth on synthetic biomaterials by direct measurement of GFP-specific fluorescence. To simplify operations, all cell cultivation steps were performed in orbitallyshaken, disposable containers. Comparative studies between this GFP assay and previously established cell quantification assays demonstrated that this novel approach is suitable for rapid screening of a large number of samples. Furthermore the utility of our assay system was confirmed by evaluation of cell growth on three polyvinylidene fluoride polymer scaffolds that differed in pore diameter and drawing conditions. The data presented here prove the general utility of GFP-expressing cell lines and orbital shaking technology for the screening of biomaterials for tissue engineering applications.

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Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts

Cited by 26 publications

References 30 publications

Induced differentiation of acute myeloid leukemia cells by activation of retinoid X and liver X receptors

Induced differentiation of acute myeloid leukemia cells by activation of retinoid X and liver X receptors

Pharmacological inhibition of the transcription factor PU.1 in leukemia

Suspension-adapted Chinese hamster ovary-derived cells expressing green fluorescent protein as a screening tool for biomaterials

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