Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes

Pattabiraman, Diwakar R., McGirr, Crystal, Shakhbazov, Konstantin, Barbier, Valerie, Krishnan, Keerthana, Mukhopadhyay, Pamela, Hawthorne, Paula, Trezise, Ann, Ding, Jianmin, Grimmond, Sean M., Papathanasiou, Peter, Alexander, Warren S., Perkins, Andrew C., Levesque, Jean-Pierre, Winkler, Ingrid G. and Gonda, Thomas J. (2014) Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes. Blood, 123 17: 2682-2690. doi:10.1182/blood-2012-02-413187

Author Pattabiraman, Diwakar R.
McGirr, Crystal
Shakhbazov, Konstantin
Barbier, Valerie
Krishnan, Keerthana
Mukhopadhyay, Pamela
Hawthorne, Paula
Trezise, Ann
Ding, Jianmin
Grimmond, Sean M.
Papathanasiou, Peter
Alexander, Warren S.
Perkins, Andrew C.
Levesque, Jean-Pierre
Winkler, Ingrid G.
Gonda, Thomas J.
Title Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2014-04-24
Year available 2014
Sub-type Article (original research)
DOI 10.1182/blood-2012-02-413187
Open Access Status DOI
Volume 123
Issue 17
Start page 2682
End page 2690
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
The MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, suggesting that MYB may be a therapeutic target in these diseases. However, realization of this potential requires a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis, and an approach for developing an effective therapeutic. We previously showed that the interaction of c-Myb with the coactivator CBP/p300 is essential for its transforming activity. Here, by using cells from Booreana mice which carry a mutant allele of c-Myb, we show that this interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type mice, Booreana cells transduced with AML1-ETO9a or MLL-AF9 retroviruses fail to generate leukemia upon transplantation into irradiated recipients. Finally, we have begun to explore the molecular mechanisms underlying these observations by gene expression profiling. This identified several genes previously implicated in myeloid leukemogenesis and HSC function as being regulated in a c-Myb p300-dependent manner. These data highlight the importance of the c-Myb-p300 interaction in myeloid leukemogenesis and suggest disruption of this interaction as a potential therapeutic strategy for acute myeloid leukemia.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Wed, 21 May 2014, 23:04:10 EST by Susan Allen on behalf of Institute for Molecular Bioscience