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Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome–like acute lymphoblastic leukemia in humans
https://repo.qst.go.jp/records/86025
https://repo.qst.go.jp/records/8602508b30a8e-7654-4621-9d99-ae4bbbeb3d90
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-12-03 | |||||
| タイトル | ||||||
| タイトル | Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome–like acute lymphoblastic leukemia in humans | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Hirotaka, Tachibana
× Hirotaka, Tachibana× Kazuhiro, Daino× Atsuko, Ishikawa× Takamitsu, Morioka× Yi, Shang× Mari, Ogawa× Akira, Matsuura× Yoshiya, Shimada× Shizuko, Kakinuma× Hirotaka, Tachibana× Kazuhiro, Daino× Atsuko, Ishikawa× Takamitsu, Morioka× Yi, Shang× Mari, Ogawa× Yoshiya, Shimada× Shizuko, Kakinuma |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Epidemiological studies have revealed a radiation-related increase in the risk of developing acute lymphoblastic leukemia (ALL). Our recent study revealed early induction and increased risk of precursor B-cell (pB) lymphomas in mice after radiation exposure. However, the genomic landscape of radiation-induced B-cell lymphomas remains unclear. To identify the relevant genetic alterations in mice, whole-exome sequencing was performed on both early-onset and late-onset B-cell lymphomas that developed spontaneously or after gamma-irradiation. In addition to multiple driver mutations, the data revealed that interstitial deletion of chromosome 4, including Pax5, and missense mutations in Jak3 are unique genomic alterations in radiation-induced, early-onset B-cell lymphomas. RNA sequencing revealed a pB-cell-type gene-expression profile with no involvement of known fusion genes for human ALLs in the early-onset B-cell lymphomas. Activation of Jak3/Stat5 signaling in early-onset B-cell lymphomas was validated using western capillary electrophoresis. Those features were similar to those of Philadelphia chromosome–like ALL. Our data suggest a critical role for Pax5 loss-of-function mutations in initiating B-cell leukemogenesis coupled with activation of Jak3/Stat5 signaling as a basis for the rapid development of radiation-induced pB-ALL. These molecular signatures for radiation-induced cancers will inform both risk assessment and potential targeted therapies for pB-ALL. | |||||
| 書誌情報 |
Carcinogenesis 発行日 2022-04 |
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| 出版者 | ||||||
| 出版者 | Oxford University Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1460-2180 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 35395675 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/carcin/bgac034. | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://academic.oup.com/carcin/advance-article/doi/10.1093/carcin/bgac034/6565633?login=true | |||||
