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

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:

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

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>