Acute myelogenous leukemia (AML) cells represent a state of impaired differentiation, enhanced growth and survival of the myeloid progenitors. The tight correlation between cytogenetic alterations and response to therapy is indicative of a cause and effect relationship between the genotype and the disease phenotype. Acquired partial or complete deletion of the long arm of chromosome 7 (7q- or -7) seen in 22% of AML cases, constitutes the most common Cytogenetic anomaly and is associated with poor prognosis. The limits of the interstitial 7q deletions may vary from patient to patient, however there are critical regions of overlap that are consistently deleted. We hypothesize an important role for conversion to hemizygosity at these loci in the evolution of the abnormal phenotype. The studies described here are aimed at understanding the biology and clinical course of the disease in patients with poor prognosis. Our investigations will aim at: l) Molecular delineation of the critical regions of loss in chromosome 7 by loss of heterozygosity analyses; 2) Isolation of genomic clones for the critical loci from a normal human genomic library in Yeast Artificial Chromosome vector; 3) Long range restriction map of the clones isolated in #2 and search for rearrangements of the critical loci in poor prognosis patients; 4) a) Determination of the stage of myeloid maturation at which the anomalies of chromosomes 5 and 7 occur; and b) Comparison of growth factor and chemotherapy response in vitro and in vivo of patients with poor prognosis. A correlation will be made between the genotype of chromosomes 5 and 7 loci and the response to therapy. These studies will provide clues on the molecular mechanisms underlying the refractoriness seen in patients with abnormalities of chromosome 5 and 7.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055164-08
Application #
6102711
Study Section
Project Start
1999-06-07
Project End
2000-03-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
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
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
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

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