Featured Research

from universities, journals, and other organizations

Discovery Offers New Avenues To Understanding An Aggressive Form Of Leukemia

Date:
April 15, 2008
Source:
St. Jude Children's Research Hospital
Summary:
Researchers have discovered evidence that a series of genetic mutations work together to initiate most cases of an aggressive and often-fatal form of acute lymphoblastic leukemia.

Researchers at St. Jude Children‘¦s Research Hospital have discovered evidence that a series of genetic mutations work together to initiate most cases of an aggressive and often-fatal form of acute lymphoblastic leukemia (ALL).

Related Articles


These defects, known as "cooperating oncogenic lesions," include the deletion of a gene, IKZF1, whose protein, Ikaros, normally helps guide the development of a blood stem cell into a lymphocyte. The researchers also found that loss of the same gene accompanied the transformation of chronic myelogenous leukemias (CMLs) to a life-threatening acute stage.

"These findings provide new avenues to pursue to gain a better understanding of these disease processes and, ultimately, to develop better therapies," said James R. Downing, M.D., St. Jude scientific director and chair of the Department of Pathology.

The new study, which he and his colleagues reported in the advance online publication of the journal "Nature," adds further support to a key concept in cancer genetics: Malignancies frequently require mutations in multiple genes in order to develop.

Cells contain oncogenes, which exist harmlessly until something triggers them to turn the cells malignant.

"It really takes a series of genetic lesions to lead to cancer," Downing said. "You may get activation of an oncogene, but you may also need activation of a tumor suppressor gene and an alteration in a cell-death pathway."

St. Jude researchers sought to identify genetic differences between CML and a form of acute leukemia known as BCR-ABL1ƒ{positive ALL.

Both diseases are characterized by the Philadelphia chromosome, which results from the translocation (joining) of parts of two different chromosomes. The result of this translocation is the expression of BCR-ABL1, an oncogene.

"It appears from our study, and other work published previously, that all you need to get CML is that chromosomal translocation and BCR-ABL1 expression," Downing said.

In their new study, the researchers re-examined the genetic makeup of 304 ALL patients who had been studied earlier. The group included 43 pediatric and adult BCR-ABL1 ALL patients and 23 adults with CML. Using a more sensitive technology, the scientists increased the number of genetic mutations found in their original gene survey.

In the first study, the gene most commonly altered was one called PAX5, followed by a gene designated IKZF1. Its protein, Ikaros, is involved in the development and differentiation of B lymphocyte cells, which are part of the immune system.

"The vast majority of pediatric acute lymphoblastic leukemias are of B-cell lineage," Downing said.

Among the ALL patients, the researchers found an average of 8.79 copy number alterations, a form of genetic change linked to the development and progression of cancer. The most common change was deletion of the gene for Ikaros.

The gene was deleted in 36 (83.7 percent) of the BCR-ABL1 ALL patients, including 76.2 percent of the pediatric and 90.9 percent of the adult cases.

"The loss of the Ikaros gene is a nearly obligatory lesion for the development of BCR-ABL1 ALL," Downing said, "and clearly must be a genetic lesion that is cooperating with BCR-ABL1."

Moreover, a gene known as CDKN2A was deleted in 53.5 percent of the BCR-ABL1 ALL patients, 87.5 percent of whom also had lost the gene for Ikaros. The PAX5 deletion occurred in 51 percent of the BCR-ABL1 ALL patients; and 95 percent of these people were missing the Ikaros gene.

Among the CML patients whose disease converted to ALL, two out of three had the deletion of the Ikaros gene; a lower percentage of those who converted to acute myeloblastic leukemia had the same gene deleted. That finding suggested that the deletion of Ikaros is cooperating with BCR-ABL1 to cause ALL.

"That is an important finding that may give insight into how that transformation occurs, or it may give insight into a better way to treat the disease, if one can figure out how the Ikaros deletion is working," Downing said.

Other authors of this paper include Charles Mullighan, Christopher Miller, Ina Radtke, Letha Phillips, James Dalton, Jing Ma, Ching-Hon Pui, Mary Relling, Sheila Shurtleff (St. Jude); Deborah White and Timothy Hughes (The Institute for Medical and Veterinary Science, Adelaide, Australia); and Michelle Le Beau (University of Chicago, Ill.).

This work was supported by ALSAC. Mullighan was supported by grants from the National Health and Medical Research Council, the Royal Australasian College of Physicians and the Haematology Society of Australasia.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Discovery Offers New Avenues To Understanding An Aggressive Form Of Leukemia." ScienceDaily. ScienceDaily, 15 April 2008. <www.sciencedaily.com/releases/2008/04/080414113203.htm>.
St. Jude Children's Research Hospital. (2008, April 15). Discovery Offers New Avenues To Understanding An Aggressive Form Of Leukemia. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2008/04/080414113203.htm
St. Jude Children's Research Hospital. "Discovery Offers New Avenues To Understanding An Aggressive Form Of Leukemia." ScienceDaily. www.sciencedaily.com/releases/2008/04/080414113203.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) — Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) — Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) — Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins