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Disorders of the cMyb proto-oncogene expression and its significance in the course of ATL development

Accumulation of genetic disorders in HTLV-1 infected cells underlies ATL leukemogenesis, yet the actual genetic events responsible for cellular transformation have not been fully elucidated. Based on gene expression profiling in 52 ATL patients, 40 HTLV-1 carriers, and 21 healthy volunteers, we determined several potential risk-indicator genes of ATL, including cMyb. cMyb is the proto-oncogene of vMyb, the oncoprotein of avian myeloblastosis virus, governing hematopoietic cell differentiation. Required for differentiation of DN3, survival of DP, and generation of CD4+-SP cells, cMyb is not expressed at a detectable level in mature T-cells. Among well-known 7 isoforms, cMyb-9A and -10A, lacking the cis-acting negative regulatory domain (NRD) same as vMyb oncoprotein, are known to be molecules of “gain of oncogenic function”. We demonstrated that the mRNA levels of cmyb-9a and -10a were drastically elevated in ATL cells. Moreover, cMyb-9A protein was overexpressed in PBMC of HTLV-1 carriers and ATL patients. cMyb-9A showed the highest transactivation of HTLV-1 LTR, which is one of the cMyb targets, among 7 isoforms. The level of cMyb is known to be regulated by SUMOylation through the NRD. As expected, SUMOylation assay showed that cMyb-9A was not effectively SUMOylated, and its activity was not suppressed. Finally, cMyb-9A exhibited a significantly higher transforming activity than WT-cMyb. Upon confirming that cMyb-9A is released from the negative-regulatory circuit of cMyb, we speculate that overexpression of cMyb-9A in HTLV-1 infected cells has a strong link to disorders in cellular homeostasis by overruling its target gene expression, thus accelerating transformation process to ATL.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Nakano, K., Utsunomiya, A., Yamaguchi, K. et al. Disorders of the cMyb proto-oncogene expression and its significance in the course of ATL development. Retrovirology 11 (Suppl 1), P94 (2014).

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