Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover normal version of molecular pathway affected in poor-prognosis childhood leukemia

07.06.2013
Through genetic engineering of laboratory models, researchers at Dartmouth-Hitchcock Norris Cotton Cancer Center have uncovered a vulnerability in the way cancer cells diverge from normal regenerating cells that may help treat children with leukemia as reported in the journal PNAS on June 3, 2013.
Dartmouth researchers are trying to understand the key pathways that distinguish how a normal blood cell grows and divides compared to the altered growth that occurs in leukemia. In addition to the treatment of leukemia, the work has relevance for expanding umbilical cord blood or bone marrow stem cells for transplantation.

Leukemia often occurs due to chromosomal translocations, which are broken chromosomes that cause blood cells to grow uncontrollably. One gene that is involved in chromosomal translocations found at high frequency in childhood leukemia is the MLL1 (Mixed Lineage Leukemia 1) gene. Conventional chemotherapy is very ineffective at curing patients with this translocation, in contrast to other types of childhood leukemia, which are relatively curable.

Using genetic engineering, the researchers generated a mouse model to discover genes that are regulated by MLL1 in hematopoietic stem cells, the cells that give rise to all white and red blood cell types. In the course of these studies, they identified several unique properties of the normal MLL1 pathway in hematopoietic stem cells that may be exploited to better treat leukemia harboring MLL1 translocations.

"We discovered that many genes that depend upon the normal MLL1 protein are involved in maintaining hematopoietic stem cells, thus manipulating this pathway could be a way to expand cells from normal bone marrow or umbilical cord blood donors to improve transplantation of these cell types, which is a procedure used to treat certain chemotherapy-resistant cancers," said Patricia Ernst, PhD, co-director Cancer Mechanisms, Dartmouth-Hitchcock Norris Cotton Cancer Center, associate professor of Genetics and of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, Hanover, NH.

As principle investigator, Ernst and her team set out to discover the genetic pathways controlled by the normal form of the MLL1 protein and leukemogenic MLL1 fusion proteins specifically in hematopoietic stem cells (HSCs). Delineation of these pathways will facilitate research by her group and others aimed at developing strategies to kill leukemia cells without harming HSCs, which are often profoundly affected by current chemotherapeutic regimens. In performing this research, they also discovered a new molecular pathway that controls normal HSC biology.

"We demonstrate in this study, that some direct MLL1 target genes in HSCs are affected by Menin loss (a protein involved in the inherited disorder, Multiple Endocrine Neoplasia), and some are not," said Ernst. "This is a fundamentally important observation that demonstrates this category of chromatin modifiers utilizes different protein complexes/mechanisms to target different classes of genes in different cell types."

Ernst points out that this highly desirable outcome that would not have been predicted for this targeted therapy and may illustrate that drugs blocking the interaction of these two proteins (currently under development by other groups) leave normal hematopoiesis intact. She is working on follow-up studies of this finding.

Research funded by NIH HL090036 and RR16437 as well as additional grants from American Cancer Society, Gabrielle’s Angel Foundation for Cancer Research, Lady Tata Memorial Trust, and the Lauri Strauss Leukemia Foundation.

About Norris Cotton Cancer Center at Dartmouth-Hitchcock

Norris Cotton Cancer Center combines advanced cancer research at Dartmouth College and the Geisel School of Medicine at Dartmouth College with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center, at Dartmouth-Hitchcock regional locations in Manchester, Nashua, and Keene, NH, and St. Johnsbury, VT, and at 12 partner hospitals throughout New Hampshire and Vermont. It is one of 41 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.

For more information contact Donna Dubuc at (603) 653-3615.

Donna Dubuc | EurekAlert!
Further information:
http://www.hitchcock.org

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

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: 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 >>>