2. Academic Validation
  3. Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines

Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines

  • Sci Rep. 2020 Mar 9;10(1):4355. doi: 10.1038/s41598-020-61300-y.
Ryutaro Kotaki  # 1,  Masaharu Kawashima  # 1 2,  Yuichiro Yamamoto  # 1,  Hiroshi Higuchi 1 3,  Etsuko Nagashima 1,  Natsumi Kurosaki 1,  Masako Takamatsu 1,  Yara Yukie Kikuti 4,  Ken-Ichi Imadome 5,  Naoya Nakamura 4,  Ai Kotani 6 7 8
Affiliations

Affiliations

  • 1 Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Shimokasuya 143, Isehara, Kanagawa, Japan.
  • 2 Division of Clinical Oncology and Hematology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
  • 3 Research Institute of Science and Technology, Tokai University, 4-1-1 Kitakinme, Hiratsuka, Kanagawa, Japan.
  • 4 Department of Pathology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa, Japan.
  • 5 Department of Infectious Diseases, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
  • 6 Department of Hematological Malignancy, Institute of Medical Science, Tokai University, Shimokasuya 143, Isehara, Kanagawa, Japan. aikotani@k-lab.jp.
  • 7 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Japan. aikotani@k-lab.jp.
  • 8 AMED-PRIME, Japan Agency for Medical Research and Development, Tokyo, Japan. aikotani@k-lab.jp.
  • # Contributed equally.
PMID: 32152351 DOI: 10.1038/s41598-020-61300-y
Abstract

Latent Infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effective on EBV-positive B cell malignancies, using lymphoblastoid cell lines (LCLs) in vitro and in vivo. As a result, in vitro experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-scid/Il2rgnul (NOG) mice were treated with dasatinib. However, in vivo experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective in vitro. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV+ B cell malignancies.

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