UW 'DNA Map' Helps Identify Cause of Severe Form of Leukemia
Madison, Wisconsin - A basic science discovery in a
A new study published in Cancer Cell describes how a well-known but poorly understood gene inversion causes two percent of acute myeloid leukemia (
A single, misplaced gene can become dormant among its new surroundings, or it can become an overactive, and therefore dangerous, component of a cell’s instruction manual.
Drs. Masayuki Yamamoto, Hiromi Yamazaki and Mikiko Suzuki of
The inversion contains a
“We thought that any information on how the GATA2 gene gets turned on or turned off is going to be really important. Our initial approach led to the discovery that GATA factors themselves, namely GATA1 and GATA2, bind to some regions of the GATA2 gene, and based on our studies, we concluded that some of these regions may be very important.”
A set of publications from the Bresnick lab identified five regions (Grass et al. 2003, Martowicz et al. 2005, Grass et al. 2006). The 2006 study yielded, among others, a specific site in the chromosome termed the -77 site. That was the basis for the new study because the leukemia-associated inversion repositioned the -77 site near the EVI1 gene, which was known to be associated with human cancer.
“Cancer genomes tend to have a wide spectrum of abnormalities, so you can’t predict whether a particular rearrangement, deletion or insertion will be involved in initiation or progression of disease. But in this case, the evidence strongly suggests that the inversion causes the disease,” said Bresnick.
EVI1 is usually 40 megabases away on the chromosome from the -77 site (a megabase is 1 million units of the guanine (G), adenine (A), thymine (T) or cytosine (C) building blocks).
“Chromosomes can be several hundred megabases long, and it’s very common for a
The leukemia-associated chromosome inversion places the -77 site close to EVI1, causing EVI1 to co-opt the regulatory sequence, thereby elevating the activity of the EVI1 gene and the levels of the EVI1 protein.
Knowing the mechanism underlying the cause of this form of
Date Published: 05/19/2014