title: Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.
abstract: Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.
authors.affiliation: Institute for Advanced Research, Nagoya University, Nagoya, Japan.|Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Fujii Memorial Research Institute, Otsuka Pharmaceutical Co., Ltd, Otsu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: M
authors.identifier: 0000-0002-1838-4837
authors.initials: M
authors.lastname: Nakatochi
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suguro
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: T D
authors.initials: TD
authors.lastname: Hocking
authors.affiliation: Department of Computer Science/Scientific and Engineering Simulation, Nagoya Institute of Technology, Nagoya, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Takeuchi
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Hematology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tokunaga
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Department of Hematology, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.affiliation: Department of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Hayakawa
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.|Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Seto
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tomita
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
mesh_terms: D000368:Aged; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006085:Graft Survival; D064593:Heterografts / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D008099:Liver / Q000098:blood supply; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009928:Organ Specificity; D019043:Vascular Neoplasms / Q000473:pathology*
chemical_list: D007143:Immunoglobulin Heavy Chains