MedicineWorld.Org
Your gateway to the world of medicine
Home
News
Cancer News
About Us
Cancer
Health Professionals
Patients and public
Contact Us
Disclaimer

Medicineworld.org: Leukemic cells find safe haven

Back to cancer blog Blogs list Cancer blog  


Subscribe To Cancer Blog RSS Feed  RSS content feed What is RSS feed?

Leukemic cells find safe haven

Leukemic cells find safe haven
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, as per researchers at St. Jude Children's Research Hospital.

The scientists 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 therapy with asparaginase, a drug that normally would deplete their supply of this vital nutrient, the scientists 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 scientists 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 studys 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 well 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."

Prior 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 observed 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 Campanas 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. On the other hand, when the scientists 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.


Posted by: Janet    Source




Did you know?
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, as per researchers at St. Jude Children's Research Hospital. The scientists 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 therapy with asparaginase, a drug that normally would deplete their supply of this vital nutrient, the scientists 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.

Medicineworld.org: Leukemic cells find safe haven

Main Page| Cancer blog| Cancer blogs list| Lung cancer blog| Colon cancer blog| Prostate cancer blog| Breast cancer blog| Diabetes watch blog| Heart watch blog| Allergy blog| Bladder cancer blog| Cervical cancer blog| Colon cancer news blog| Diabetes news blog| Esophageal cancer blog| Gastric cancer blog| Health news blog| Heart news blog| Infectious disease blog| Kidney watch blog| Lung disease blog| Lung cancer news blog| Mesothelioma blog| Neurology blog| Breast cancer news blog| OBGYN blog| Ophthalmology blog| Ovarian cancer blog| Cancer news blog| Pancreas cancer blog| Pediatrics blog| Prostate cancer news blog| Psychology blog| Research blog| Rheumatology blog| Society news blog| Uterine cancer blog| Weight watch blog|

Copyright statement
The contents of this web page are protected. Legal action may follow for reproduction of materials without permission.