Abstract

MicroRNAs for the diagnosis, prognosis and treatment of AMLs We have discovered alterations of microRNA genes in human leukemias, have discovered that a large fraction of microRNA genes are in chromosomal regions involved in genomic alterations in cancers, have discovered somatic and germ line mutations of microRNA genes in leukemias, and have developed a microRNA platform to investigate the global expression of microRNA genes in normal and leukemic tissues. In addition, we have discovered that miR15/miR16 cause apoptosis by targeting BCL2 and that miR221 and 222 targetKIT. In this proposal we apply our platform to investigate the role of microRNA genes in the pathogenesis and progression of AMLs and to develop better prognostic indicators of these diseases. In addition, the identification of altered microRNA genes involved in the pathogenesis of AMLs could provide new, important targets for the development of novel therapies based on microRNAs or their antisense, depending on whether the pathogenetic microRNAs function as suppressors or oncogenes respectively. We have already made significant progress and have identified microRNAs that may play an important role in AML. This project is highly integrated with the other projects of this program and provides them with microRNA targets involved in the apoptotic process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055164-19
Application #
8334643
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
19
Fiscal Year
2011
Total Cost
$291,254
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Le, Phuong M; Andreeff, Michael; Battula, Venkata Lokesh (2018) Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis. Haematologica :
Jiang, Xuejie; Mak, Po Yee; Mu, Hong et al. (2018) Disruption of Wnt/?-Catenin Exerts Antileukemia Activity and Synergizes with FLT3 Inhibition in FLT3-Mutant Acute Myeloid Leukemia. Clin Cancer Res 24:2417-2429
Ishizawa, Jo; Nakamaru, Kenji; Seki, Takahiko et al. (2018) Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition. Cancer Res 78:2721-2731
Ruvolo, Peter P; Ruvolo, Vivian R; Burks, Jared K et al. (2018) Role of MSC-derived galectin 3 in the AML microenvironment. Biochim Biophys Acta Mol Cell Res 1865:959-969
Ngankeu, Apollinaire; Ranganathan, Parvathi; Havelange, Violaine et al. (2018) Discovery and functional implications of a miR-29b-1/miR-29a cluster polymorphism in acute myeloid leukemia. Oncotarget 9:4354-4365
Sekihara, Kazumasa; Saitoh, Kaori; Han, Lina et al. (2017) Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-1. Oncotarget 8:34552-34564
Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng et al. (2017) Focal Adhesion Kinase as a Potential Target in AML and MDS. Mol Cancer Ther 16:1133-1144
Zeng, Zhihong; Liu, Wenbin; Tsao, Twee et al. (2017) High-throughput profiling of signaling networks identifies mechanism-based combination therapy to eliminate microenvironmental resistance in acute myeloid leukemia. Haematologica 102:1537-1548
Pan, Rongqing; Ruvolo, Vivian; Mu, Hong et al. (2017) Synthetic Lethality of Combined Bcl-2 Inhibition and p53 Activation in AML: Mechanisms and Superior Antileukemic Efficacy. Cancer Cell 32:748-760.e6
Jacamo, Rodrigo; Davis, R Eric; Ling, Xiaoyang et al. (2017) Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia. Oncotarget 8:83354-83369

Showing the most recent 10 out of 422 publications