NEW YORK (Reuters Health) - Acute myeloid leukemia (AML)-associated fusion proteins cause the disease by inducing genes involved in the maintenance of the stem cell phenotype and repressing DNA repair genes. This preliminary understanding, at the molecular and biological level, may lead to more targeted treatments, suggest Italian scientists.
A team led by Dr. Myriam Alcalay from the European Institute of Experimental Oncology in Milan used DNA microarray technology to assess gene expression changes induced by three AML fusion proteins. They found 1,555 genes regulated by a least two of these fusion proteins, according to a paper in the December issue of The Journal of Clinical Investigation.
Functional studies confirmed that AML fusion protein expression activates the Jagged1/Notch pathway, leading to increased stem cell renewal, and provokes accumulation of DNA damage.
“The identification of specific proteins whose activity is altered in AMLs is of obvious importance to the possibility of identifying drug targets,” Dr. Alcalay told Reuters Health.
Next the team will try to “characterize gene expression profiles of subpopulations of leukemic stem cells, with the aim of defining the molecular signature of the ‘target cell’ of leukemic events,” Dr. Alcalay said.
They also plan to “analyze the difference at a molecular level of the ‘pre-leukemic’ phase - the latency period that elapses between fusion protein expression and frank leukemia - and the leukemic phase, with the aim of identifying secondary genetic hits,” he added.
Source: J Clin Invest 2003;112:1751-1761. [ Google search on this article ]
MeSH Headings:Leukemia, Myelocytic, Acute: Leukemia, Nonlymphocytic, AcuteCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
