Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System
ABSTRACT Background In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA‐seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clin...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70736 |
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| author | Minori Tamai Chiaki Komatsu Keiko Kagami Shin Kasai Koshi Akahane Kumiko Goi Kanji Sugita Chihiro Tomoyasu Toshihiko Imamura Hiroaki Goto Takeshi Inukai |
| author_facet | Minori Tamai Chiaki Komatsu Keiko Kagami Shin Kasai Koshi Akahane Kumiko Goi Kanji Sugita Chihiro Tomoyasu Toshihiko Imamura Hiroaki Goto Takeshi Inukai |
| author_sort | Minori Tamai |
| collection | DOAJ |
| description | ABSTRACT Background In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA‐seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clinical samples of BCP‐ALL. Cancer cell lines are powerful research tools, and thus, we built a larger series of BCP‐ALL cell lines and performed RNA‐seq analysis to confirm their utility as a model system. Methods We performed RNA‐seq in a total of 94 BCP‐ALL cell lines, including 80 cell lines with 8 representative types of translocations. Results In the UMAP visualization, a close association was confirmed between the types of fusion genes and patterns of gene expression. In the cluster analysis of the gene expression profile, each type of fusion gene showed a clear association with the expression profile in the top 51 variable genes. Of clinical importance, the majority of the top variable genes in the BCP‐ALL cell lines also showed a significant association with the types of fusion genes in the clinical samples. When an association of 125 cell cycle‐related genes with the percentage of S and G2/M phases in 67 cell lines was evaluated, a significant positive correlation with cell cycle progression was confirmed in 10 cell cycle‐related genes (HDAC2, CDC23, YWHAG, MAD2L1, CCNH, ANAPC7, CDC6, ANAPC5, ORC3, andRBX1). Moreover, significant upregulation and downregulation of 40 and 10 genes, respectively, were observed in the cell lines established at relapse compared with those established at diagnosis. Four (SP6, CCNE1, HIST1H2BH, and DECR2) and two (EVI2B and SYN1) of these genes were also significantly higher and lower, respectively, in the clinical samples at relapse than in those at diagnosis. Conclusion Large series of BCP‐ALL cell lines is a powerful research tool for studying the mechanisms of leukemogenesis and the disease progression of BCP‐ALL. |
| format | Article |
| id | doaj-art-71d85f47e87847a0b545d42c01a80c9b |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-71d85f47e87847a0b545d42c01a80c9b2025-08-20T02:05:21ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70736Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model SystemMinori Tamai0Chiaki Komatsu1Keiko Kagami2Shin Kasai3Koshi Akahane4Kumiko Goi5Kanji Sugita6Chihiro Tomoyasu7Toshihiko Imamura8Hiroaki Goto9Takeshi Inukai10Global Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanDepartment of Pediatrics University of Yamanashi Yamanashi JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanDepartment of Pediatrics Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto JapanDepartment of Pediatrics Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto JapanHematology/Oncology Kanagawa Children's Medical Center Kanagawa JapanGlobal Leukemia Cell‐Line Assembly Network University of Yamanashi Yamanashi JapanABSTRACT Background In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA‐seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clinical samples of BCP‐ALL. Cancer cell lines are powerful research tools, and thus, we built a larger series of BCP‐ALL cell lines and performed RNA‐seq analysis to confirm their utility as a model system. Methods We performed RNA‐seq in a total of 94 BCP‐ALL cell lines, including 80 cell lines with 8 representative types of translocations. Results In the UMAP visualization, a close association was confirmed between the types of fusion genes and patterns of gene expression. In the cluster analysis of the gene expression profile, each type of fusion gene showed a clear association with the expression profile in the top 51 variable genes. Of clinical importance, the majority of the top variable genes in the BCP‐ALL cell lines also showed a significant association with the types of fusion genes in the clinical samples. When an association of 125 cell cycle‐related genes with the percentage of S and G2/M phases in 67 cell lines was evaluated, a significant positive correlation with cell cycle progression was confirmed in 10 cell cycle‐related genes (HDAC2, CDC23, YWHAG, MAD2L1, CCNH, ANAPC7, CDC6, ANAPC5, ORC3, andRBX1). Moreover, significant upregulation and downregulation of 40 and 10 genes, respectively, were observed in the cell lines established at relapse compared with those established at diagnosis. Four (SP6, CCNE1, HIST1H2BH, and DECR2) and two (EVI2B and SYN1) of these genes were also significantly higher and lower, respectively, in the clinical samples at relapse than in those at diagnosis. Conclusion Large series of BCP‐ALL cell lines is a powerful research tool for studying the mechanisms of leukemogenesis and the disease progression of BCP‐ALL.https://doi.org/10.1002/cam4.70736BCP‐ALLcell cyclechemoresistanceleukemogenesisrelapseRNA‐seq |
| spellingShingle | Minori Tamai Chiaki Komatsu Keiko Kagami Shin Kasai Koshi Akahane Kumiko Goi Kanji Sugita Chihiro Tomoyasu Toshihiko Imamura Hiroaki Goto Takeshi Inukai Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System Cancer Medicine BCP‐ALL cell cycle chemoresistance leukemogenesis relapse RNA‐seq |
| title | Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System |
| title_full | Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System |
| title_fullStr | Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System |
| title_full_unstemmed | Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System |
| title_short | Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System |
| title_sort | utility of a large series of b cell precursor acute lymphoblastic leukemia cell lines as a model system |
| topic | BCP‐ALL cell cycle chemoresistance leukemogenesis relapse RNA‐seq |
| url | https://doi.org/10.1002/cam4.70736 |
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