The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias
Open accessAbstract
Summary We created a mouse model where conditional expression of an Mll-AF4 fusion oncogene induces B-precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 Lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. Human MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We have thus demonstrated that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4 driven gene expression. Significance The t(4;11) encodes an MLL-AF4 fusion protein, and predicts a particularly poor prognosis when found in acute lymphoblastic leukemias (ALL). Recent studies suggest certain MLL-fusion proteins enhance gene expression by recruitment of the histone H3 lysine79 (H3K79) methyltransferase DOT1L. We demonstrate that H3K79 methylation is enhanced at many loci in leukemia cells from a murine model of Mll-AF4 and in human MLL-AF4 leukemia cells and this elevation is correlated with enhanced gene expression. Furthermore, suppression of H3K79 methylation leads to inhibition of gene expression in MLL-AF4 cells. These data demonstrate that inhibition of DOT1L may be a therapeutic approach in this disease, and that this mouse model should be useful for assessment of therapeutic approaches for MLL-rearranged ALL.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9
Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., et al. (2006) · Nature · doi:10.1038/nature04980 · Cited by 1,513 · cited 3×
“This analysis identified a number of genes previously associated with MLLrearranged leukemias, including HOXA genes, MEIS1, RUNX2, PROM1, and FLT3 (Figures 6C and 6D; Figure S6B) (Armstrong et al., 2002, 2003; Krivtsov and Armstrong, 2007; Krivtsov et al., 2006; Rozovskaia et al., 2001).”
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Cited by
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia
Zuber, J., Shi, J., Wang, E., Rappaport, A. R., Herrmann, H., Sison, E. A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., et al. (2011) · Nature · doi:10.1038/nature10334 · Cited by 1,870
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339
Writing, erasing and reading histone lysine methylations
Hyun, K., Jeon, J., Park, K., & Kim, J. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.11 · Cited by 1,250
Xiao, M., Yang, H., Xu, W., Ma, S., Lin, H., Zhu, H., Liu, L., Liu, Y., Yang, C., Xu, Y., et al. (2012) · Genes & Development · doi:10.1101/gad.191056.112 · Cited by 1,188
“To further substantiate the above results, we determined mRNA expression of Hoxa genes whose up-regulation is associated with increased H3K79 dimethylation in MLL rearranged mouse leukemia and human AML patients (Krivtsov et al. 2008).”
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Metadata
- Authors
- Krivtsov, A. V., Feng, Z., Lemieux, M. E., Faber, J., Vempati, S., Sinha, A. U., Xia, X., Jesneck, J., Bracken, A. P., Silverman, L. B., Kutok, J. L., Kung, A. L., & Armstrong, S. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 14
- Issue
- 5
- Pages
- 355-368
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1977729188
- Cited by
- 550
- References
- 2
- FWCI
- 38.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Krivtsov, A. V., Feng, Z., Lemieux, M. E., Faber, J., Vempati, S., Sinha, A. U., Xia, X., Jesneck, J., Bracken, A. P., Silverman, L. B., Kutok, J. L., Kung, A. L., & Armstrong, S. A. (2008). H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias. Cancer Cell. https://doi.org/10.1016/j.ccr.2008.10.001
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