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 Potential seen for tailoring treatment for acute myeloid leukemia
10.12.2018 | University of Washington Health Sciences/UW Medicine

nachricht UC San Diego researchers develop sensors to detect and measure cancer's ability to spread
06.12.2018 | University of California - San Diego

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: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Small but ver­sat­ile; key play­ers in the mar­ine ni­tro­gen cycle can util­ize cy­anate and urea

10.12.2018 | Life Sciences

New method gives microscope a boost in resolution

10.12.2018 | Physics and Astronomy

Carnegie Mellon researchers probe hydrogen bonds using new technique

10.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>