Study suggests improved treatment alternative for lymphoid leukemia

February 11, 2013, Cincinnati Children's Hospital Medical Center

Discovering what they call the "Achilles' heel" for lymphoid leukemia, an international research team has tested a possible alternative treatment that eradicated the disease in mouse models.

Reporting their results Feb. 11 in the journal Cancer Cell, the scientists said the targeted molecular therapy described in their study could have direct implications for current treatment of Acute Lymphoid (ALL) in people.

Led by researchers at Cincinnati Children's Hospital Medical Center and the Institut de recherches cliniques de Montreal (ICRM), the study found that depend on a protein called Gfi1 for survival. Removing the protein in mouse models of the disease weakened and killed the . Researchers said this should make the leukemia more susceptible to chemo and – the current frontline treatments for ALL.

"Chemo and radiation therapies are very non-specific and can be toxic to patients. Our findings suggest that combining the inhibition of Gfi1 with these treatments may allow the use of lower cytotoxic doses and directly benefit patients," said H. Leighton Grimes, PhD, co-senior investigator on the study and researcher in the divisions of Cellular and Molecular Immunology and Experimental Hematology at Cincinnati Children's.

Also collaborating was co-senior investigator, Tarik Möröy, PhD, president and scientific director of the ICRM in Montreal.

The researchers said the need for better treatment options is evident. Beside the potential toxicity of current therapeutic options, many ALL patients relapse after initial remission of their disease.

A cancer that affects and the immune system, ALL is the most common type of leukemia in children from infancy up to age 19, according to the Leukemia and Lymphoma Society of America. ALL occurs most often in the first decade of life but increases in frequency again in older individuals. According to the , the overall survival rate for all ages of people with ALL is 66.4 percent and 90.8 percent for children under the age of 5 years.

During the onset of a disease like ALL, cancer signals among cells activate a protein called p53, which is often referred to as the "guardian of the genome." A repressor of tumor growth, p53 normally initiates a DNA repair program that is supposed to induce programmed cell death to stop or slow down tumor progression.

In the case of ALL, the researchers said the disease relies on the Gfi1 protein to get around p53's tumor repressing capabilities by essentially overriding p53. Gfi1 has an important role in the normal development of lymphoid cells. But analyses of ALL mouse models and primary human tumors showed that Gfi1 is overexpressed in the disease state.

When the researchers removed Gfi1 in established mouse lymphoid tumors, the leukemia regressed through p53-induced cell death. Next, to see if removal of Gfi1 would be effective in modeled human ALL, the research team inserted T-cell leukemia cells from human patients into mice. Inhibiting Gfi1 in this instance stopped the progression of human leukemia in the animals without any harmful effects.

The scientists are continuing their research to see if results of the current study will be translatable to human patients.

Explore further: Therapy targets leukemia stem cells

Related Stories

Therapy targets leukemia stem cells

February 13, 2012
New research takes aim at stubborn cancer stem cells that are thought to be responsible for treatment resistance and relapse. The study, published by Cell Press in the February 14 issue of the journal Cancer Cell, provides ...

Researchers discover rare leukemia-causing protein

July 2, 2012
Researchers at the University of Cincinnati (UC) Hoxworth Blood Center have discovered a new gene target for leukemia therapy.

Researcher pieces together AML prognosis puzzle

October 15, 2012
When patients suffering from Acute Myeloid Leukemia (AML) express high levels of the gene, MN1, an already aggressive leukemia is accelerated and shortens survival time. While that's a known fact, the mechanisms involved ...

Recommended for you

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.

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 ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018
The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of ...

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.