Washington, Mar 2 : Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have identified a new mechanism capable to boost the function of a protein, known as AML1 that is usually weakened in patients with acute forms of leukemia.
AML1 is a crucial factor in the development of the blood system and in the production of platelets and immune cells.
In the study, led by Stephen D. Nimer, MD, Chief of the Hematology Service at MSKCC, the researchers identified the methyltransferase enzyme that controls the activity of the normal AML1 protein, also called RUNX1. They also showed how it could regulate the function of transcription factors, proteins that control cell fate by turning genes on or off.
It was discovered that the cellular pathways controlling the activity of the normal AML1 protein through a process called arginine methylation, cannot similarly regulate the activity of AML1-ETO, a protein associated with causing acute leukemia.
In the process of Methylation, methyltransferases catalyze the attachment of a methyl group to DNA or protein for regulating gene expression or protein function. However, enzymes called demethylase, that remove methyl groups from proteins, have only recently been discovered.
"By manipulating the activity of these enzymes, it may be possible to promote the activity of the normal protein, and thereby lessen the impact of the protein that promotes leukaemia. We are just beginning to explore whether we can tilt the balance toward a normally functioning AML1 protein in leukemic cells and either trigger their death or their reversion to normal behavior," said Nimer.
Currently, no drugs are available to target protein methylation, although FDA has approved two drugs that target DNA methylation for treating patients with myelodysplastic syndromes.
"We hope to utilize these new findings to help develop and ultimately test new treatment strategies for patients with either myeloid or lymphoid types of acute leukemia," said Xinyang Zhao, a member of Dr. Nimer's laboratory.
The findings of this study are published in the recent issue of Genes and Development.