3D Model Characterization by 2D and 3D Imaging in t(14;18)-Positive B-NHL: Perspectives for In Vitro Drug Screens in Follicular Lymphoma
Fabien Gava
(1, 2, 3, 4)
,
Carla Faria
(1, 2, 3, 4)
,
Pauline Gravelle
(1, 2, 3, 4)
,
Juan Valero
(5, 6)
,
Cèlia Dobaño-López
(5, 6)
,
Renaud Morin
(7)
,
Marine Norlund
(7)
,
Aurélie Gomes
(7)
,
Jean-Michel Lagarde
(7)
,
Cédric Rossi
(8)
,
Julie Bordenave
(1, 2, 3, 4)
,
Laetitia Pieruccioni
(9)
,
Jacques Rouquette
(9)
,
Alba Matas-Céspedes
(5, 6)
,
Jean-Jacques Fournié
(1, 2, 3, 4)
,
Loïc Ysebaert
(1, 2, 3, 4)
,
Camille Laurent
(1, 2, 3, 4)
,
Patricia Pérez-Galán
(5, 6)
,
Christine Bezombes
(1, 2, 3, 4)
1
CRCT -
Centre de Recherches en Cancérologie de Toulouse
2 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
3 Laboratoire d’Excellence ‘TOUCAN’ [Toulouse]
4 CALYM - Institut Carnot Lymphome
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 CIBERO - Centro de Investigación Biomedica en Red de Oncologia [Pamplona, Spain]
7 Imactiv-3D
8 CHU Dijon
9 RESTORE - Geroscience and rejuvenation research center
2 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
3 Laboratoire d’Excellence ‘TOUCAN’ [Toulouse]
4 CALYM - Institut Carnot Lymphome
5 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
6 CIBERO - Centro de Investigación Biomedica en Red de Oncologia [Pamplona, Spain]
7 Imactiv-3D
8 CHU Dijon
9 RESTORE - Geroscience and rejuvenation research center
Carla Faria
- Fonction : Auteur
- PersonId : 1174299
- IdRef : 264915364
Pauline Gravelle
- Fonction : Auteur
- PersonId : 948576
- ORCID : 0000-0002-0462-5652
- IdRef : 176934472
Juan Valero
- Fonction : Auteur
- PersonId : 809841
- ORCID : 0000-0003-3193-9099
- IdRef : 152708995
Cèlia Dobaño-López
- Fonction : Auteur
- PersonId : 809842
- ORCID : 0000-0001-9248-9883
Alba Matas-Céspedes
- Fonction : Auteur
- PersonId : 809843
- ORCID : 0000-0003-2121-2793
Jean-Jacques Fournié
- Fonction : Auteur
- PersonId : 178841
- IdHAL : jean-jacques-fournie
- ORCID : 0000-0001-6542-6908
- IdRef : 031095887
Loïc Ysebaert
- Fonction : Auteur
- PersonId : 806931
- ORCID : 0000-0001-8478-5623
- IdRef : 06931151X
Patricia Pérez-Galán
- Fonction : Auteur
- PersonId : 784831
- ORCID : 0000-0003-3895-5024
Christine Bezombes
- Fonction : Auteur
- PersonId : 870021
- ORCID : 0000-0003-4079-4872
- IdRef : 157707199
Résumé
Follicular lymphoma (FL) is an indolent B cell lymphoproliferative disorder of transformed follicular center B cells, which accounts for 20–30 percent of all non-Hodgkin lymphoma (NHL) cases. Great advances have been made to identify the most relevant targets for precision therapy. However, no relevant models for in vitro studies have been developed or characterized in depth. To this purpose, we generated a 3D cell model from t(14;18)-positive B-NHL cell lines cultured in ultra-low attachment 96-well plates. Morphological features and cell growth behavior were evaluated by classical microscopy (2D imaging) and response to treatment with different drugs was evaluated by a high-content analysis system to determine the robustness of the model. We show that the ultra-low attachment (ULA) method allows the development of regular, spherical and viable ULA-multicellular aggregates of lymphoma cells (MALC). However, discrepancies in the results obtained after 2D imaging analyses on drug-treated ULA-MALC prompted us to develop 3D imaging and specific analyses. We show by using light sheet microscopy and specifically developed 3D imaging algorithms that 3D imaging and dedicated analyses are necessary to characterize morphological properties of 3D models and drug effects. This study proposes a new method, but also imaging tools and informatic solutions, developed for FL necessary for future preclinical studies.