Open AccessEstablishment and characterization of a novel vincristine‐resistant diffuse large B‐cell lymphoma cell line containing the 8q24 homogeneously staining region
Author(s) -
Mizuno Shohei,
Hanamura Ichiro,
Ota Akinobu,
Karnan Sivasundaram,
Kanasugi Jo,
Nakamura Ayano,
Takasugi Souichi,
Uchino Kaori,
Horio Tomohiro,
Goto Mineaki,
Murakami Satsuki,
Gotou Mayuko,
Yamamoto Hidesuke,
Watarai Masaya,
Shikami Masato,
Hosokawa Yoshitaka,
Miwa Hiroshi,
Taniwaki Masafumi,
Ueda Ryuzo,
Nitta Masakazu,
Takami Akiyoshi
Publication year - 2018
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12538
Subject(s) - vincristine , staining , cell culture , lymphoma , line (geometry) , cell , characterization (materials science) , microbiology and biotechnology , biology , chemistry , pathology , medicine , biochemistry , materials science , genetics , nanotechnology , chemotherapy , geometry , mathematics , cyclophosphamide
Chromosome band 8q24 is the most frequently amplified locus in various types of cancers. MYC has been identified as the primary oncogene at the 8q24 locus, whereas a long noncoding gene, PVT 1 , which lies adjacent to MYC , has recently emerged as another potential oncogenic regulator at this position. In this study, we established and characterized a novel cell line, AMU ‐ ML 2, from a patient with diffuse large B‐cell lymphoma (DLBCL), displaying homogeneously staining regions at the 8q24 locus. Fluorescence in situ hybridization clearly detected an elevation in MYC copy numbers corresponding to the homogenously staining region. In addition, a comparative genomic hybridization analysis using high‐resolution arrays revealed that the 8q24 amplicon size was 1.4 Mb, containing the entire MYC and PVT 1 regions. We also demonstrated a loss of heterozygosity for TP 53 at 17p13 in conjunction with a TP 53 frameshift mutation. Notably, AMU ‐ ML 2 cells exhibited resistance to vincristine, and cell proliferation was markedly inhibited by MYC ‐sh RNA ‐mediated knockdown. Furthermore, genes involved in cyclin D, mTOR , and Ras signaling were downregulated following MYC knockdown, suggesting that MYC expression was closely associated with tumor cell growth. In conclusion, AMU ‐ ML 2 cells are uniquely characterized by homogenously staining regions at the 8q24 locus, thus providing useful insights into the pathogenesis of DLBCL with 8q24 abnormalities.