All blood cell production in adults depends on the steady work of a vital gene that if lost results in early bone marrow failure, Dartmouth Medical School cancer geneticists have found. Their research reveals an unexpected role for the gene in sustaining the adult blood-forming system, and opens novel strategies for targeting the gene, which is often involved in a type of childhood leukemia.
“We have identified a new pathway that is essential for blood stem cell turnover,“ said team leader Dr. Patricia Ernst, assistant professor of genetics and member of the Norris Cotton Cancer Center. The pathway could be exploited for treating a rare but aggressive infant leukemia, she added. These findings were reported in the September issue of Cell Stem Cell.
The investigators created a mouse model to track the function of a gene called MLL, which stands for Mixed Lineage Leukemia. The gene acts in bone marrow stem cells and controls key aspects of their growth to generate all the mature blood cells. If disrupted, it cannot work properly, and leukemia can ensue.
“MLL is the most commonly affected gene in childhood leukemia in children under a year of age; this particular type of leukemia has one of the worst success rates with the existing cancer therapies,” said Ernst, who first helped clarify the role of MLL as a postdoctoral fellow at Harvard.
Many childhood leukemias result from mutations called translocations, where gene pieces on chromosomes accidentally relocate and misalign. In infant leukemia, the chromosome containing the MLL gene breaks within MLL and ends up fused to a different gene. MLL fusion genes likely co-opt normal MLL functions in blood cells, leading to the overproduction of white cells and leukemia.
Previous studies indicated that MLL is critical for embryonic blood stem cell development, but its role for the adult system was unknown. In their mouse model, the researchers found that bone marrow failure occurred as early as 14 days after they induced the experimental loss of MLL, demonstrating the crucial role of MLL as “necessary for both the development and maintenance of the body’s blood supply,” according to the researchers.
“We have shown that the adult blood-forming system depends on the continuous actions of MLL,” Ernst said. Moreover, with the mouse model the scientists established to define normal MLL functions, they can begin exploring how to craft new anti-cancer treatments, she pointed out. “We and other groups can start designing targeted therapies that inhibit cancerous forms of MLL that occur in childhood leukemia and do not affect normal MLL function, which, based on our studies in mice, would be fatal for the patient.”
Hali Wickner | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
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...
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...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy