Scientists decode epigenetic mechanisms distinguishing stem cell function and blood cancer

May 9, 2014, The Geisel School of Medicine at Dartmouth
Scientists decode epigenetic mechanisms distinguishing stem cell function and blood cancer
Patricia Ernst, PhD

Researchers at Dartmouth's Norris Cotton Cancer Center have published results from a study in Cell Reports that discovers a new mechanism that distinguishes normal blood stem cells from blood cancers.

"These findings constitute a significant advance toward the goal of killing without harming the body's normal which are often damaged by chemotherapy," said Patricia Ernst, PhD, co-director of the Cancer Mechanisms Program of the Norris Cotton Cancer Center and an associate professor in Genetics at the Geisel School of Medicine.

The study focused on a pathway regulated by a gene called MLL1 (for Mixed Lineage Leukemia). Ernst served as principal investigator; Bibhu Mishra, PhD, as lead author.

When the MLL1 gene is damaged, it can cause , which is a cancer of the blood, often occurring in very young patients. Researchers found that the normal version of the gene controls many other genes in a manner that maintains the production of blood cells.

"This control becomes chaotic when the gene is damaged or 'broken' and that causes the normal blood cells to turn into leukemia," said Ernst.

The researchers showed that the normal gene acts with a partner gene called MOF that adds small "acetyl" chemical modification around the genes that it controls. The acetyl modification acts as a switch to turn genes on. When this function is disrupted, MLL1 cannot maintain normal blood stem cells.

The researchers also found that a gene called Sirtuin1 (more commonly known for controlling longevity) works against MLL1 to keep the proper amount of "acetyl" modifications on important stem cell genes. Blood cancers involving MLL1, in contrast, do not have this MOF-Sirtuin balance and place a different on that result in leukemia.

Blood stem cells also represent an important therapy for patients whose own stem cells are destroyed by chemotherapy. This study also reveals a new way to treat blood stem cells from donors that would expand their numbers.

"These finding suggest that drugs that block Sirtuin1 may be combined with MLL1 blocking drugs in certain leukemia to both preserve that make normal blood at the same time as killing leukemia cells," said Ernst.

Explore further: Researchers discover normal molecular pathway affected in poor-prognosis childhood leukemia

More information: Paper: http://www.cell.com/cell-reports/fulltext/S2211-1247(14)00302-7

Related Stories

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

June 6, 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 ...

A promising new approach for treating leukemia discovered

February 13, 2014
A group of researchers at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal discovered a promising new approach to treating leukemia by disarming a gene that is responsible for tumor progression. ...

Rare form of leukemia found to originate in stem cells

February 13, 2014
(Medical Xpress)—An international team of researchers working out of the University of Toronto has found that one type of rare leukemia appears to get its start in stem cells. In their paper published in the journal Nature, ...

Pushing the boundaries of stem cells

May 7, 2014
Adults suffering from diseases such as leukemia, lymphoma, and other blood-related disorders may benefit from life-saving treatment commonly used in pediatric patients. Researchers at the Icahn School of Medicine at Mount ...

Major breakthrough in developing new cancer drugs: Capturing leukemic stem cells

March 18, 2014
The Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal (UdeM), in collaboration with the Maisonneuve-Rosemont Hospital's Quebec Leukemia Cell Bank, recently achieved a significant breakthrough ...

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.