Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma

K. Shimada, S. Shimada, K. Sugimoto, M. Nakatochi, M. Suguro, A. Hirakawa, T. D. Hocking, I. Takeuchi, T. Tokunaga, Y. Takagi, A. Sakamoto, T. Aoki, T. Naoe, S. Nakamura, F. Hayakawa, M. Seto, Akihiro Tomita, H. Kiyoi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1568-1579
Number of pages12
JournalLeukemia
Volume30
Issue number7
DOIs
Publication statusPublished - 01-07-2016

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B-Cell Lymphoma
Heterografts
Neoplasms
Adrenal Glands
Cell Biology
Cell Migration Inhibition
Serial Passage
Gene Expression Profiling
Bone Marrow Cells
Cell Movement
Blood Cells
B-Lymphocytes
Cell Proliferation
Liver
Genes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Shimada, K., Shimada, S., Sugimoto, K., Nakatochi, M., Suguro, M., Hirakawa, A., ... Kiyoi, H. (2016). Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. Leukemia, 30(7), 1568-1579. https://doi.org/10.1038/leu.2016.67
Shimada, K. ; Shimada, S. ; Sugimoto, K. ; Nakatochi, M. ; Suguro, M. ; Hirakawa, A. ; Hocking, T. D. ; Takeuchi, I. ; Tokunaga, T. ; Takagi, Y. ; Sakamoto, A. ; Aoki, T. ; Naoe, T. ; Nakamura, S. ; Hayakawa, F. ; Seto, M. ; Tomita, Akihiro ; Kiyoi, H. / Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. In: Leukemia. 2016 ; Vol. 30, No. 7. pp. 1568-1579.
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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.",
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Shimada, K, Shimada, S, Sugimoto, K, Nakatochi, M, Suguro, M, Hirakawa, A, Hocking, TD, Takeuchi, I, Tokunaga, T, Takagi, Y, Sakamoto, A, Aoki, T, Naoe, T, Nakamura, S, Hayakawa, F, Seto, M, Tomita, A & Kiyoi, H 2016, 'Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma', Leukemia, vol. 30, no. 7, pp. 1568-1579. https://doi.org/10.1038/leu.2016.67

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. / Shimada, K.; Shimada, S.; Sugimoto, K.; Nakatochi, M.; Suguro, M.; Hirakawa, A.; Hocking, T. D.; Takeuchi, I.; Tokunaga, T.; Takagi, Y.; Sakamoto, A.; Aoki, T.; Naoe, T.; Nakamura, S.; Hayakawa, F.; Seto, M.; Tomita, Akihiro; Kiyoi, H.

In: Leukemia, Vol. 30, No. 7, 01.07.2016, p. 1568-1579.

Research output: Contribution to journalArticle

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AU - Shimada, K.

AU - Shimada, S.

AU - Sugimoto, K.

AU - Nakatochi, M.

AU - Suguro, M.

AU - Hirakawa, A.

AU - Hocking, T. D.

AU - Takeuchi, I.

AU - Tokunaga, T.

AU - Takagi, Y.

AU - Sakamoto, A.

AU - Aoki, T.

AU - Naoe, T.

AU - Nakamura, S.

AU - Hayakawa, F.

AU - Seto, M.

AU - Tomita, Akihiro

AU - Kiyoi, H.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

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Shimada K, Shimada S, Sugimoto K, Nakatochi M, Suguro M, Hirakawa A et al. Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. Leukemia. 2016 Jul 1;30(7):1568-1579. https://doi.org/10.1038/leu.2016.67