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:4/28/2016)... First quarter 2016:   , ... the first quarter of 2015 The gross margin was ... 18.8) and the operating margin was 40% (-13) Earnings ... flow from operations was SEK 249.9 M (21.2) , ... SEK 7,000-8,500 M. The operating margin for 2016 is ...
(Date:4/15/2016)... April 15, 2016 Research ... Gait Biometrics Market 2016-2020,"  report to their offering.  ... ) , ,The global gait biometrics market is ... during the period 2016-2020. Gait analysis ... can be used to compute factors that are ...
(Date:3/29/2016)... 2016 LegacyXChange, Inc. (OTC: ... SelectaDNA/CSI Protect are pleased to announce our successful effort ... variety of writing instruments, ensuring athletes signatures against counterfeiting ... from athletes on LegacyXChange will be assured of ongoing ... Bill Bollander , CEO states, "By ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... April 27, 2016 , ... PathSensors, Inc., ... Advisory Board. Dr. Lamka will assist PathSensors in expanding the use of the ... deploys the CANARY® test platform for the detection of harmful pathogens, including a ...
(Date:4/27/2016)... April 27, 2016 MedDay, a biotechnology ... announces the appointment of Catherine Moukheibir as Chairman of its ... Chairman, Jean Jacques Garaud , who contributed to the ... effective immediately. Catherine started her career in strategy ... and London .  She held C-Suite level ...
(Date:4/26/2016)... CAMBRIDGE, Mass. (PRWEB) , ... April 26, 2016 , ... ... Herr has been selected as one of three finalists for the European Inventor ... the EPO’s annual innovation prize will be announced at a ceremony in Lisbon on ...
(Date:4/26/2016)... ... April 26, 2016 , ... BioFactura, Inc ., a ... round of financing. Healthy investor interest drove significant oversubscription of the original $1.5M ... known as biosimilars, to the advanced preclinical stages. , Chief Executive Officer and President, ...
Breaking Biology Technology: