Truncated c-Myb expression in the human leukemia cell line TK-6

A. Tomita, T. Watanabe, H. Kosugi, H. Ohashi, T. Uchida, T. Kinoshita, S. Mizutani, T. Hotta, T. Murate, M. Seto, H. Saito

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The c-MYB proto-oncogene encodes a transcription factor which plays an important role in hematopoiesis. We detected truncated c-MYB mRNA (2.0 kb) and c-Myb protein (55 kDa) in the TK-6 cell line, which was established from a patient with chronic myelogenous leukemia in T cell blast crisis. Mutated c-MYB cDNA clone (WTK-1) was isolated from a TK-6 cell cDNA library and sequenced in its entirety. Compared with the wild-type human c-MYB sequence, the WTK-1 sequence diverged at the 3' ends of exons 9. A termination codon was present as the second codon downstream from the point of divergence and was followed by a previously unknown rearranged sequence. The conceptual protein encoded by WTK-1 (Myb(TK-6)) comprises 402 amino acids and lacks the negative regulatory domain of the normal c-Myb, reminiscent of the activated form of Myb protein. Luciferase reporter assay in NIH3T3 cells showed that the expression vector encoding Myb(TK-6) stimulated Myb-regulated mim-1 promoter more effectively than that encoding wild-type human c-Myb, suggesting that Myb(TK-6) is functional as a transcription factor, and thus as a potential transforming protein. Southern blot and mutant allele-specific polymerase chain reaction analyses showed that the same rearrangement of the c-MYB gene in TK-6 was present in late, but not in early, specimens obtained from the patient, indicating that this mutation had been acquired during disease progression.

元の言語English
ページ(範囲)1422-1429
ページ数8
ジャーナルLeukemia
12
発行部数9
DOI
出版物ステータスPublished - 1998

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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    Tomita, A., Watanabe, T., Kosugi, H., Ohashi, H., Uchida, T., Kinoshita, T., Mizutani, S., Hotta, T., Murate, T., Seto, M., & Saito, H. (1998). Truncated c-Myb expression in the human leukemia cell line TK-6. Leukemia, 12(9), 1422-1429. https://doi.org/10.1038/sj.leu.2401113