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The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

DOT1L, the H3K79 methyltransferase, is required for MLL-AF9–mediated leukemogenesis

Open access
Nguyen, Anh Tram, Taranova, Olena, He, Jin, Zhang, Yi·2011·Blood

Abstract

Chromosomal translocations of the mixed lineage leukemia (MLL) gene are a common cause of acute leukemias. The oncogenic function of MLL fusion proteins is, in part, mediated through aberrant activation of Hoxa genes and Meis1, among others. Here we demonstrate using a tamoxifen-inducible Cre-mediated loss of function mouse model that DOT1L, an H3K79 methyltransferase, is required for both initiation and maintenance of MLL-AF9–induced leukemogenesis in vitro and in vivo. Through gene expression and chromatin immunoprecipitation analysis we demonstrate that mistargeting of DOT1L, subsequent H3K79 methylation, and up-regulation of Hoxa and Meis1 genes underlie the molecular mechanism of how DOT1L contributes to MLL-AF9–mediated leukemogenesis. Our study not only provides the first in vivo evidence for the function of DOT1L in leukemia, but also reveals the molecular mechanism for DOT1L in MLL-AF9 mediated leukemia. Thus, DOT1L may serve as a potential therapeutic target for the treatment of leukemia caused by MLL translocations.

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Metadata

Authors
Nguyen, A. T., Taranova, O., He, J., & Zhang, Y.
Venue
Blood
Published
2011-06-23
Volume
117
Issue
25
Pages
6912-6922
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2059171174
Cited by
275
References
48
FWCI
11.70
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: DOT1L, the H3K79 methyltransferase, is required for MLL-AF9–mediated leukemogenesis. https://app.cochat.ai/papers/10.1182/blood-2011-02-334359
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Nguyen, A. T., Taranova, O., He, J., & Zhang, Y. (2011). DOT1L, the H3K79 methyltransferase, is required for MLL-AF9–mediated leukemogenesis. Blood. https://doi.org/10.1182/blood-2011-02-334359

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