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Manzotti G, Mariani SA, Corradini F, et al. Expression of p89(c-Mybex9b), an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells. Blood Cancer J. 2012;2(5):e71doi: 10.1038/bcj.2012.16.
Manzotti, G., Mariani, S. A., Corradini, F., Bussolari, R., Cesi, V., Vergalli, J., Ferrari-Amorotti, G., Fragliasso, V., Soliera, A. R., Cattelani, S., Raschellà, G., Holyoake, T. L., & Calabretta, B. (2012). Expression of p89(c-Mybex9b), an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells. Blood cancer journal, 2(5), e71. https://doi.org/10.1038/bcj.2012.16
Manzotti, G, et al. "Expression of p89(c-Mybex9b), an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells." Blood cancer journal vol. 2,5 (2012): e71. doi: https://doi.org/10.1038/bcj.2012.16
Manzotti G, Mariani SA, Corradini F, Bussolari R, Cesi V, Vergalli J, Ferrari-Amorotti G, Fragliasso V, Soliera AR, Cattelani S, Raschellà G, Holyoake TL, Calabretta B. Expression of p89(c-Mybex9b), an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells. Blood Cancer J. 2012 May;2(5):e71. doi: 10.1038/bcj.2012.16. Epub 2012 May 11. PMID: 22829973; PMCID: PMC3366069.
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Blood Cancer J. 2012 May;2(5):e71. doi: 10.1038/bcj.2012.16. Epub 2012 May 11.

Expression of p89(c-Mybex9b), an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells.

Blood cancer journal

G Manzotti, S A Mariani, F Corradini, R Bussolari, V Cesi, J Vergalli, G Ferrari-Amorotti, V Fragliasso, A R Soliera, S Cattelani, G Raschellà, T L Holyoake, B Calabretta

PMID: 22829973 PMCID: PMC3366069 DOI: 10.1038/bcj.2012.16

Abstract

The c-Myb gene encodes the p75(c-Myb) isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is p(c-Mybex9b), which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein-protein interactions and negative regulation. In hematopoietic cells, expression of p(c-Mybex9b) accounts for 10-15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of p(c-Mybex9b) and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75(c-Myb), p(c-Mybex9b) is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of p(c-Mybex9b) enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of p(c-Mybex9b) reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34(+) cells, without affecting the levels of p75(c-Myb). Together, these studies indicate that expression of the low-abundance p(c-Mybex9b) isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells.

Keywords: chronic myeloid leukemia; oncogene; transcription factor

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