Abstract
We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.
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Acknowledgements
This work was supported by grants from the Foundation Against Cancer (a public interest foundation) (J.C.), the Fonds voor Wetenschappelijk Onderzoek (FWO)-Vlaanderen (P.M., F.S.), the Interuniversity Attraction Poles granted by the Belgian Federal Office for Scientific, Technical and Cultural Affairs, a José Carreras fellowship from the European Hematology Association (J.C.), Concerted Research Action grant 12051203 (F.S.), the Sophia Foundation for Medical Research (SSWO-404, P.V.V.), the Spanish Association Against Cancer (I.L., M.D.O.) and a Concerted Research Action Grant from K.U. Leuven (J.C., P.V., I.W., P.M.). I.L. is a visiting postdoctoral researcher, K.D.K. is an aspirant, J.C. is a postdoctoral researcher and P.V. is a clinical investigator of the FWO-Vlaanderen. M.B. is funded by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-Vlaanderen).
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I.L., K.D.K., P.V.V., J.P.P.M. and J.C. designed the study; I.L., K.D.K., P.V.V., C.G., B.C., N.M., I.W. and J.P.P.M. performed experiments and data analysis; C.G., F.L., H.B.B., R.P., F.S., M.D.O., M.B., G.F., P.V. and J.P.P.M. provided material and I.L., K.D.K., P.V.V., J.P.P.M., P.M., P.V., I.W. and J.C. contributed to writing of the paper.
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Supplementary information
Supplementary Fig. 1
FISH detects MYB duplication. (PDF 862 kb)
Supplementary Table 1
Copy number of MYB and flanking genes in individuals and cell lines with MYB duplication. (PDF 139 kb)
Supplementary Table 2
Cytogenetic and molecular characteristics of individuals with T-ALL with MYB duplication. (PDF 119 kb)
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Lahortiga, I., De Keersmaecker, K., Van Vlierberghe, P. et al. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Nat Genet 39, 593–595 (2007). https://doi.org/10.1038/ng2025
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DOI: https://doi.org/10.1038/ng2025
