Decoding an ALL Mighty Cancer

B acute lymphoblastic leukemia biomarkers and therapeutic targets identified

(RxWiki News) One type of blood cancer is fairly common in children. It’s called acute lymphoblastic leukemia, or ALL for short. Most children are cured of this cancer. In adults, though, ALL is far more ferocious.

ALL is a cancer of the bone marrow and blood. This cancer interferes with the body’s white blood cells - key members of the immune system that fight off bacteria and other invaders.

Scientists have identified new biomarkers that can predict the severity of adult B-acute lymphoblastic leukemia. They have also pinpointed targets that new drugs can attack to treat the disease.

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Ari Melnick, MD, associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College, and colleagues conducted the study.

It’s known that the more genetic mutations adults with this leukemia have, the poorer the outlook. Dr. Melnick’s team sought to identify and isolate the key biological changes that can result in more serious and fatal forms of B-acute lymphoblastic leukemia, which strikes about 6,000 adult Americans a year.

Researchers studied 215 tissue samples gathered from adult patients with the disease who were enrolled in a large Eastern Cooperative Oncology Group phase III clinical trial.

The scientists looked at what’s known as epigenetic changes, which are alterations in how the DNA is modified and packaged. Epigenetic changes can lead to the start and growth of cancer.

Another way of looking at this is to think of the researchers decoding the key "software" instructions of ALL.

The team learned that epigenetic changes were involved in keeping leukemic cells alive and thriving. They also found that one molecule that’s seen on the surface of cells - CD25 – predicts poorer outlook for B-acute lymphoblastic leukemia patients.

"Finding the instructions that ultimately lead to cancer development, and to the especially bad outcome seen in patients with these different forms of ALL, is especially urgent. Our study is the first to integrate the decoding of many layers simultaneously, which has enabled us to unlock some of the mysteries explaining the malignant and aggressive behavior of these leukemias," said Dr. Melnick, who is also a hematologist-oncologist at New York-Presbyterian Hospital/Weill Cornell Medical Center.

Reprogrammed leukemia cells were shown to activate a powerful oncoprotein (cancer protein) – BCL6, which Dr. Melnick said, “was an extremely powerful indicator of the presence of the most aggressive and fatal cases.”

"We then designed inhibitors of BCL6 and showed that we could kill leukemia cells from patients enrolled in the clinical trial by blocking its function," Melnick continued.

These findings have led researchers to plan to use CD25 as a biomarker for patients with the most serious cases in upcoming clinical trials, and to personalize treatment as appropriate.

The BCL6 blockers are being developed for human use. Researchers hope to design clinical trials that specifically target BCL6 in specific forms of this ALL.

"These results will ultimately lead to biomarkers that help guide treatment and to the development of therapies that will be more effective for patients with this aggressive form of leukemia," Melnick said.

Findings from this study were published October 29 in Cancer Discovery, a journal of the American Association for Cancer Research.

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Review Date: 
November 8, 2012