Navigation Links
Tracking the molecular pathway to mixed-lineage leukemia
Date:12/15/2008

CAMBRIDGE, Mass. (Dec. 15, 2008) Infants and adults with the blood cancer mixed-lineage leukemia (MLL) typically have a poor prognosis, and most infants die before their first birthdays. Although there are varying causes of MLL, most cases are caused by a fusion of two genes, the MLL and the AF4 genes.

When the MLL gene is fused to the AF4 gene, a potent cancer-causing oncogene is created. Although researchers have known that the MLL-AF4 protein produced by this genetic fusion causes leukemia, they had not been able to determine precisely how this oncogene disrupted cells' normal protein production.

To pinpoint the oncogene's activities, Matthew Guenther, a postdoctoral researcher in Whitehead Member Richard Young's lab, used a technique called ChIP-seq (chromatin immunoprecipitation with DNA sequencing) to map where the MLL-AF4 protein interacts with a cell's genome. He found that in cancer cells the MLL-AF4 protein binds to at least 169 genes, many of which are overexpressed in leukemia cells and encode hematopoietic stem cell regulators (the genes that initiate blood cell production).

It seems that when the MLL-AF4 protein interacts with these genes, it forces them into a hyperactive state, with disastrous consequences.

"The MLL-AF4 fusion protein is somehow targeted to a set of genes that essentially hijacks the blood stem cell machinery and makes that cell become cancerous, basically a younger-looking cell that is dividing much more than it should," says Guenther.

Looking closer at the MLL-AF4 protein-bound genes, Guenther noticed that these genes display strange patterns of chromatin proteins. In the cell, DNA is wrapped around chromatin proteins for dual purposes: to safely package DNA for cell division and to control gene expression (epigenetics). Changes in chromatin structures can affect normal gene expression, and other studies have linked chromatin misregulation to cancer and to leukemia disease progression. In MLL patients, it seems the MLL-AF4 protein alters the normal chromatin state of the hematopoietic stem cell regulators.

Guenther's findings may take scientists one step closer to a treatment for this deadly disease.

"We think we've figured out a key piece of how this leukemia works," says Young. "If we understand the molecular pathway for how the MLL-AF4 protein interacts with genes, it gives us a set of new target genes that might be used for drug development."


'/>"/>

Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. Tracking feline memories on the move
2. Louisiana Tech researchers investigate tracking, sensors to assist Air Force
3. NIH recognizes Clemson nanotechnology for molecule tracking
4. GestureTek/Imagination Launch AirPoint, Worlds First Hand-Tracking Unit, for Shell Group.
5. Tracking stroke
6. Tracking influenzas every movement
7. Tracking prions
8. Paleozoic sediment curve provides new tool for tracking sea-floor sediment movements
9. Tracking down the cause of mad cow disease
10. Scientists achieve first tracking of salmon from headwaters in Rockies through Pacific to Alaska
11. Oral rinses used for tracking HPV-positive head and neck cancers holds promise for cancer screening
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/22/2017)... Optimove , provider of the ... as 1-800-Flowers and AdoreMe, today announced two new ... Using Optimove,s machine learning algorithms, these features allow ... recommendations to their customers based not just on ... intent drawn from a complex web of data ...
(Date:3/16/2017)... Germany , March 16, 2017 CeBIT 2017 - Against identity ... Continue Reading ... Used combined in one project, multi-biometric solutions provide ... Used ... Systems) ...
(Date:3/7/2017)... , March 7, 2017 Brandwatch , the ... by The Prince,s Trust to uncover insights to support ... The Trust. The UK,s leading youth charity will be ... campaign results and get a better understanding of the topics and ... ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... March 23, 2017 According to a report ... derivatives market is fragmented due to the presence of a large pool ... Thermo Fisher , and Sigma-Aldrich, compete with each other in ... collectively, held more than 76% of this market in 2016.  ... As of now, a ...
(Date:3/23/2017)... ... March 23, 2017 , ... ... today announced the hire of Dr. Sigmund “Sig” Floyd as Vice President ? ... partnerships and joint development activities. , “Dr. Floyd’s career has spanned 30 years ...
(Date:3/22/2017)... 2017  Ascendis Pharma A/S (Nasdaq: ASND), a ... to address significant unmet medical needs in rare ... year ended December 31, 2016. ... as we broadened our pipeline and pursued our ... company with an initial focus on endocrinology," said ...
(Date:3/22/2017)... 2017 Oramed Pharmaceuticals Inc. (NASDAQ: ... ), a clinical-stage pharmaceutical company focused ... announced today that Dr. Miriam Kidron , ... titled, "Oral Insulin for Diabetes Treatment: Bypassing the ... and Peptide Therapeutics (OPT) Boston Conference in ...
Breaking Biology Technology: