Mice lacking both copies of the Arid4A gene and one copy of the Arid4B gene develop acute myeloid leukemia (AML) and may provide an important animal model for preleukemic and leukemic conditions, according to an article in the Aug. 26 online issue of the Journal of the National Cancer Institute.
It is well known that genetic mutations, which alter the sequence of DNA in chromosomes, can lead to cancer. More recently, researchers have found that changes in chromatin structure and activity (epigenetic changes) can lead to cancer as well. The Arid4 family of genes is involved in chromosome remodeling, but their impact on leukemia was not known.
Arthur Beaudet, M.D., of Baylor College of Medicine in Houston and colleagues bred mice that lacked both copies of Arid4A and one copy of Arid4B. They monitored the animals' health through repeated blood cell counts and molecular tests on blood and bone marrow cells.
The mutant mice developed a myeloproliferative disorder that resembled chronic myeloid-monocytic leukemia. The animals then progressed to AML. The pattern of disease progression in the animals resembled the course of events in humans and may indicate that the mutant mice are useful models for studying how AML develops and testing potential therapeutics.
"Further study of the Arid4 gene family may advance our understanding of the connection between gene regulation, epigenetic control, disease development, and cancer formation," the authors write. "We also suggest that gene regulation by the ARID4A and ARID4B should be examined for potential disease-related roles, not only in human malignancies, but also in other complex disease traits."
- Mei-Yi Wu, Karen W. Eldin, and Arthur L. Beaudet. Identification of Chromatin Remodeling Genes Arid4a and Arid4b as Leukemia Suppressor Genes. Journal of the National Cancer Institute, 2008; DOI: 10.1093/jnci/djn253
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