Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Leukemic cells find safe haven in bone marrow

St. Jude study shows mesenchymal cells in bone marrow supply leukemic cells with the amino acid asparagine, restoring this critical nutrient when it is depleted by the cancer drug asparaginase

The cancer drug asparaginase fails to help cure some children with acute lymphoblastic leukemia (ALL) because molecules released by certain cells in the bone marrow counteract the effect of that drug, according to investigators at St. Jude Children's Research Hospital.

The researchers showed that mesenchymal cells in the bone marrow create a protective niche for leukemic cells by releasing large amounts of asparagine, an amino acid that nearby leukemic cells must have to survive but do not make efficiently. This extra supply of asparagine helps leukemic cells survive treatment with asparaginase, a drug that normally would deplete their supply of this vital nutrient, the researchers reported. Mesenchymal cells give rise to a variety of different tissues, such as osteoblasts (bone-building cells) and chondrocytes (cartilage-building cells), and form the nurturing environment where normal blood cells and leukemic cells grow.

"Leukemic cells that resist asparaginase and survive in this protective niche of the bone marrow might be the reason that leukemia recurs in some children who have been treated with this drug," said Dario Campana, M.D., Ph.D., a member of the St. Jude Oncology and Pathology departments.

Campana is senior author of the report that appears in the online pre-publication issue of "The Journal of Clinical Investigation."

"Our findings indicate that the level of activity of the "ASNS" gene in the mesenchymal cells is key to protecting leukemic cells in the bone marrow from asparaginase," Campana said. "This insight will help researchers find ways to disrupt this safe haven for leukemic cells that need asparagine," added James R. Downing, M.D., St. Jude scientific director and chair of the Pathology department. Downing is a co-author of "The Journal of Clinical Investigation" paper. The "ASNS" gene controls production of the enzyme asparagine synthetase (ASNS), which leukemic cells use to make asparagine.

The study’s findings also suggest that drugs now being developed to block ASNS should be tested to see if they also prevent mesenchymal cells from making this amino acid. In addition, the ability of mesenchymal cells to make asparagine might be decreased by cancer drugs that are already known to disrupt the activity of those cells.

"Because asparaginase is so widely used to treat ALL, this new insight into how mesenchymal cells protect leukemic cells is very important," said Ching-Hon Pui, M.D., chair of the Oncology department and American Cancer Society Professor at St. Jude. "The more we learn about the molecular interactions between these cells, the more likely we’ll be able to enhance the anti-leukemic action of asparaginase and perhaps other anti-leukemic drugs as well," said Pui, a co-author of the paper. "That would reduce the recurrence rate of ALL and continue our successful efforts to increase the survival rate of ALL."

Previous research at St. Jude and elsewhere had shown that direct contact with bone marrow mesenchymal cells is essential for the long-term survival and multiplication of leukemic lymphoblasts. In the current study, the team found that the gene for ASNS was more than 20 times active in producing this enzyme in mesenchymal cells than in ALL cells.

Experiments performed by co-authors Shotaro Iwamoto, M.D., and Keichiro Mihara, postdoctoral fellows in Campana’s laboratory, demonstrated that ALL cells from different patients became much more resistant to asparaginase when cultured on top of a layer of mesenchymal cells. In order to determine whether it was the high levels of asparagine released by mesenchymal cells that protected ALL cells from asparaginase, the St. Jude team repeated the experiment, but blocked the ability of mesenchymal cells to make the ASNS enzyme and produce asparagine. In this case, the protective effect of mesenchymal cells was eliminated. Conversely, when the researchers caused the ASNS gene to work overtime making asparagine, the ability of the mesenchymal cells layer to protect the ALL cells was significantly enhanced. The team also showed that the more actively "ASNS" genes produced ASNS in mesenchymal cells, the higher levels of asparagine they released.

Summer Freeman | EurekAlert!
Further information:

Further reports about: ASNS Protect asparaginase asparagine leukemic marrow mesenchymal

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

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

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>