Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find gene that causes leukemia in children with Down syndrome

12.08.2002


Researchers from the University of Chicago have identified a gene defect that causes the development of leukemia in children with Down syndrome. The discovery, scheduled for Advance Online Publication on Nature Genetics’s website on 12 August, could speed diagnosis and provide a new target for therapy.



Children with Down syndrome are 10 to 20 times as likely as unaffected children to develop leukemia. They most commonly develop a type known as acute megakaryoblastic leukemia (AMKL), which is extremely rare in children without Down syndrome.

"This study, for the first time, defines a part of the molecular pathway leading to acute megakaryoblastic leukemia," said John Crispino, Ph.D., assistant professor in the Ben May Institute for Cancer Research at the University of Chicago and director of the study. "Having three copies of chromosome 21 places children with Down syndrome at increased risk for leukemia, then this abnormality tips the balance toward AMKL."


"This is a rare malignancy," added co-author Michelle Le Beau, Ph.D., professor of medicine at the University, "but a great deal of what we now know about the molecular basis of cancer has come from disorders like this. Our finding pinpoints a specific pathway that leads to this kind of cancer, offers a method for rapid and precise diagnosis, and suggests more focused ways to treat this disease."

Unlike most studies, which begin with a disease then search for the genetic trigger, this one began with a suspect gene. Crispino’s laboratory had been interested in a gene called GATA1 for years because it played a role in the maturation of blood cells.

Dr. Crispino hypothesized that GATA1 might be mutated or dysregulated in leukemia. He contacted Le Beau, an expert on the genetics of leukemia. After they identified a patient with Down syndrome who had a mutation in GATA1 and had acute megakaryoblastic leukemia in a small pilot study they began searching for other patients with childhood leukemia and an abnormal copy of this gene.

When they looked at DNA from 75 patients with various types of myeloid leukemia and 21 healthy people, they found that six out of six patients with Down syndrome and acute megakaryoblastic leukemia had an alteration in GATA1. None of the other patients surveyed had an abnormal version of this gene.

GATA1 is a transcription factor; it controls the expression of other genes. It normally functions to regulate genes that control the production of red blood cells and platelets, which enable the blood to carry oxygen and to clot. Previous studies in mice had shown that the loss of GATA1 caused the cells that give rise to platelets to proliferate excessively.

The abnormal GATA1 gene, found in the leukemia patients, produces a protein with a piece missing. The incomplete protein appears to be far less effective in regulating target genes, resulting in an outcome that is similar to having no GATA1 protein at all.

"GATA1 is just part of the story," said Crispino, "but it is a crucial early step that should lead us to the rest of the pathway." The authors suspect that it requires several gene abnormalities working in tandem to cause full-fledged acute megakaryoblastic leukemia and they are searching for the other genes that combine with GATA1 to trigger this disease.


Funding for this study was provided by the Burroughs Wellcome Foundation, the Aplastic Anemia and MDS International Foundation, the Cancer Research Foundation and the Picower Foundation. Additional authors include Joshua Wechsler, Marianne Greene and John Anastasi of the University of Chicago; Michael McDevitt of Johns Hopkins University; and Judith Karp of the University of Maryland.

John Easton | EurekAlert!

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Structured light and nanomaterials open new ways to tailor light at the nanoscale

23.04.2018 | Physics and Astronomy

On the shape of the 'petal' for the dissipation curve

23.04.2018 | Physics and Astronomy

Clean and Efficient – Fraunhofer ISE Presents Hydrogen Technologies at the HANNOVER MESSE 2018

23.04.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>