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. 2021 Apr;193(2):415-419.
doi: 10.1111/bjh.17372. Epub 2021 Mar 9.

Preclinical characterisation and development of a novel myelodysplastic syndrome-derived cell line

Sahba Shafiee  1   2 , Pascal Gelebart  1 , Mihaela Popa  2   3 , Monica Hellesøy  2 , Randi Hovland  4 , Rakel Brendsdal Forthun  3 , Jungwoo Lee  5 , Kaoru Tohyama  6 , Anders Molven  7   8 , Biju Parekkadan  9 , Bjørn Tore Gjertsen  1   2   3   10 , Astrid Olsnes Kittang  1   3 , Emmet McCormack  1   2   10
Affiliations

Preclinical characterisation and development of a novel myelodysplastic syndrome-derived cell line

Sahba Shafiee et al. Br J Haematol. 2021 Apr.
No abstract available

Keywords: MDS-L; MDS-L-2007; MDS-LGF; NSG mice; NSGS mice; hydrogel scaffold; myelodysplastic syndromes (MDS); xenograft mouse model.

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Conflict of interest statement

Conflicts of interests

Bjørn Tore Gjertsen has received consultant honoraria and grants support from BerGenBio, Seattle Genetics, Novartis, Astellas Pharma, Speakers’ Bureau, from Pfizer and research funding from Boehringer Ingelheim. Gjertsen has stock and ownership interests in Alden Cancer Therapy II and KinN Therapeutics AS. Emmet Mc Cormack has stock and ownership interests in KinN Therapeutics AS. Mihaela Popa and Sahba Shafiee are employees of KinN Therapeutics AS. The remaining authors declare no conflicts of interest.

Figures

Fig 1.
Fig 1.
Development and characterisation of MDS-L-2007 and MDS-LGF sublines. (A) NSGS immunodeficient mice were injected intravenously with 5 × 106 MDS-L-2007 (n = 5) or MDS-LGF (n = 5) luciferase-expressing cell lines and imaged by bioluminescence weekly. Sample data from one mouse per group are presented. (B) Quantification of total bioluminescent flux from luciferase-expressing cell lines in weeks 1 to 9 post injection. (C) NSG (n = 5) and NSGS (n = 5) animals were injected intravenously with 5 × 106 MDS-L-2007 cells and evaluated for survival based on the Kaplan–Meier method; results of the Mantel–Cox log-rank test are shown. (D) Mass cytometric analysis of MDS-L sublines MDS-L-2007 and MDS-LGF with a panel of several monoclonal antibodies against cell surface markers and the proliferation marker Ki67 with all values. (E) Fluorescence in situ hybridisation (FISH) analysis of chromosome 5q, in n = 279 counted MDS-LGF, and (F) n = 272 MDS-L-2007 cells. 2G2R are cases with normal 5q with two green and two red, and 2G1R, direct loss of heterozygosity (del5q). (G) Cytokine expression of in vitro cultures of MDS-L-2007 and MDS-LGF versus blank controls was determined and data are represented as standard error of the mean (SEM) ± mean, by unpaired Student’s t-test on GraphPad prism version 7 (GraphPad Software, San Diego, CA, USA). Individual groups were compared using an unpaired t-test, *P < 0.05; **P < 0 01; ***P < 0.001.
Fig 2.
Fig 2.
Development of an MDS xenograft model based on MDS-LGF cells. (A) Growth of MDS-LGF [1 × 105 cells expressing green fluorescent protein (GFP) and luciferase] either suspended in Matrigel® and loaded into hydrogel scaffolds (+) or culture media (−) was monitored and quantified (B) in vitro by bioluminescence imaging at the times indicated. (C) Luciferase-expressing MDS-LGF cells (5 × 106) were loaded into hydrogel scaffolds (n = 16) in Matrigel®, implanted subcutaneously in NSG (n = 8) and NSGS (n = 8) mice and imaged weekly. (D) Quantification of total bioluminescent flux for NSG (n = 8) and NSGS (n = 8) mice implanted subcutaneously with hydrogel scaffolds loaded with 5 × 106 MDS-LGF cells in Matrigel®. (E) Mass cytometric analysis of in vitro cultures and ex vivo-recovered MDS-LGF cells from hydrogel scaffolds. Statistical analysis was performed by using an unpaired Student’s t-test to compare the differences between individual groups, *P value < 0.05; **P value < 0.01; ***P value < 0.001.
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References

    1. Dotson JL, Lebowicz Y. Myelodysplastic syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020. - PubMed
    1. Lowenberg B. Introduction to a review series on myelodysplastic syndromes. Blood. 2019;133(10):1001. - PubMed
    1. Kim T, Moon JH, Lee YJ, Tyndel M, Ahn J-S, Kim H-J, et al. Longitudinal tracking of MDS patients using next generation sequencing provides a predictive measure for Azacitidine response and AML progression. Blood. 2016;128(22):52–52.
    1. Nazha A. The MDS genomics-prognosis symbiosis. Hematology Am Soc Hematol Educ Program. 2018;2018(1):270–6. - PMC - PubMed
    1. Hayashi Y, Zhang Y, Yan X, Sashida G, Xu Z, Dong Y, et al. Novel myelodysplastic syndromes-like mouse models by cooperating genetic/epigenetic mutations reveal the critical role of HIF-1a for disease development. Blood. 2014;124(21):362–362.

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