Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

St. Jude discovery offers new avenues to understanding an aggressive form of leukemia

15.04.2008
Finding that a combination of genetic mutations can cause an aggressive form of acute lymphoblastic leukemia could lead to new cancer-fighting therapies

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).

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.

... more about:
»ALL »BCR-ABL1 »CML »Downing »IKAROS »lesion »leukemia »mutations

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.

Carrie Strehlau | EurekAlert!
Further information:
http://www.stjude.org

Further reports about: ALL BCR-ABL1 CML Downing IKAROS lesion leukemia mutations

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>