A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection

Saleh, Rosine; Wedeh, Ghaith; Herrmann, Harald; Bibi, Siham; Cerny-Reiterer, Sabine; Sadovnik, Irina; Blatt, Katharina; Hadzijusufovic, Emir; Jeanningros, Sylvie; Blanc, Catherine; Legarff-Tavernier, Magali; Chapiro, Élise; Nguyen‐Khac, Florence; Subra, Frédéric; Bonnemye, Patrick; Dubreuil, Patrice; Desplat, Vanessa; Merle-Béral, Hélène; Willmann, Michael; Rülicke, Thomas; Valent, Peter; Arock, Michel

doi:10.1182/blood-2013-10-534685

Cited by 87 publications

(121 citation statements)

References 64 publications

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“…To confirm that the effective molecular target of AQ1 were the G4 sequences in c-KIT promoter, a proliferation study was undertaken in the SCF-dependent ROSA cell line (a human mast cell line); in particular, the wild-type cell line (ROSA WT ) and its SCF-independent sub-clone ROSA KITD816V , engineered by lentiviral transfection [32] and regulated by a different promoter. In Figure 9A, the results obtained treating cells with 1 μM imatinib as a control of stable transfection are reported.…”

Section: Resultsmentioning

confidence: 99%

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models

et al. 2016

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Stabilization of G-quadruplex (G4) structures in promoters is a novel promising strategy to regulate gene expression at transcriptional and translational levels. c-KIT proto-oncogene encodes for a tyrosine kinase receptor. It is involved in several physiological processes, but it is also dysregulated in many diseases, including cancer. Two G-rich sequences able to fold into G4, have been identified in c-KIT proximal promoter, thus representing suitable targets for anticancer intervention. Herein, we screened an “in house” library of compounds for the recognition of these G4 elements and we identified three promising ligands. Their G4-binding properties were analyzed and related to their antiproliferative, transcriptional and post-transcriptional effects in MCF7 and HGC27 cell lines. Besides c-KIT, the transcriptional analysis covered a panel of oncogenes known to possess G4 in their promoters.From these studies, an anthraquinone derivative (AQ1) was found to efficiently downregulate c-KIT mRNA and protein in both cell lines. The targeted activity of AQ1 was confirmed using c-KIT–dependent cell lines that present either c-KIT mutations or promoter engineered (i.e., α155, HMC1.2 and ROSA cells).Present results indicate AQ1 as a promising compound for the target therapy of c-KIT-dependent tumors, worth of further and in depth molecular investigations.

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Section: Resultsmentioning

confidence: 99%

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models

et al. 2016

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“…1,5,6,25 The treatment eff ect is hypothesised to be a result of masitinib targeting wildtype mast cells, leading to a reduction in mast cell burden (an eff ect seen in long-term treatment of chronic myeloid leukaemia with the wild-type KIT-inhibitor imatinib; appendix p 17), 26,27 or by reducing activation of KIT Asp816Val mast cells. The latter proposed mechanism is mediated through dual inhibition of LYN and FYN, which contribute to modulation of mast cell Data are number of patients (%) aff ected.…”

Section: Discussionmentioning

confidence: 99%

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

Lortholary¹,

Chandesris²,

Livideanu³

et al. 2017

Preprint

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sitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebocontrolled, phase 3 study. The Lancet, Elsevier, 2017, 389 (10069) SummaryBackground Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and effi cacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.

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“…Purified monocytes were either used for infection assay or cultured in RPMI 1640 supplemented with granulocyte-macrophage colony-stimulating factor (2 ng/ ml) and macrophage colony-stimulating factor (20 ng/ml) for 7 days to generate monocyte-derived macrophages (MDMs). Mast cells (a gift from Michel Arock) were generated as previously described (22).…”

Section: Cell Lines and Virus Strains Hek293t Cells Hela Cells (A Gmentioning

confidence: 99%

The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection

Carnec

Meertens

Dejarnac

et al. 2016

J Virol

104

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Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection. IMPORTANCEDengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans and is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM and TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells and mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a-dependent DENV infection relies on the direct recognition of phosphatidylethanolamine and to a lesser extent PtdSer associated with viral particles. This study provides novel insights into the mechanisms that mediate DENV entry and reinforce the concept that DENV uses an apoptotic mimicry strategy for viral entry. D engue virus (DENV) belongs to the flavivirus genus, which encloses more than 70 enveloped positive-stranded RNA viruses, many of which are responsible for severe diseases in vertebrates (1, 2). There are four DENV serotypes (DENV-1, -2, -3, and -4) that are transmitted to humans by the mosquito vector Aedes aegypti. Infection with any of the DENV serotypes results in a spectrum of illness, ranging from flu-like disease (dengue fever) to more severe disease manifestations such as hemorrhagic fever and shock syndrome (3, 4). There are 390 million DENV estimated infections per year worldwide and up to 96 million dengue cases (5). No effective antiviral therapeutics or a licensed vaccine are currently available; therefore, a detailed understanding...

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A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection

Cited by 87 publications

References 64 publications

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models

Screening of candidate G-quadruplex ligands for the human c-KIT promotorial region and their effects in multiple in-vitro models

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection

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