Study shows origins of cancer that affects the blood and bone marrow

A new study from New York University Cancer Institute, NCI-designated cancer center, sheds light on the origins of myeloid leukemia, a type of blood cancer that affects children and adults. The researchers found that mutations in a novel communication channel called intracellular Notch lead to cancer, pointing to a potential new target for the treatment of this disease. Notch has been involved in another type of blood cancer called acute lymphoblastic leukemia T cells, but new research has found an unexpected role for it in myeloid leukemia.In a commentary accompanying the study in the journal Nature, Demetrios Kalaitzidis and Scott A. Armstrong Dana Farber Cancer Institute and Children’s Hospital Boston, noted that the study defines a new role as a suppressor of Notch signal developing leukemia. They note that more research is needed to understand the complexity of the Notch signal in normal tissues and tumors, which will determine “the best approaches to handling this path therapauetic best answer.”

The study evaluated mutations in the Notch pathway in mouse models of disease, and also in blood samples of patients with chronic myeloid leukemia. Researchers have identified several mutations inactivated or silenced the road, leading to accelerated accumulation of abnormal blood cells. Above all, the study also found that the reactivation of silenced genes to block the disease, providing further support for the potentially crucial role that Notch might play in cancer development.

“This study demonstrates the power of the signal path of Notch in myeloid leukemia”, said Iannis Aifantis, Ph.D., Associate Professor of Pathology at NYU Langone Medical Center and member of the NYU Cancer Institute, who led the study new. “This discovery,” he says, “suggests a potential for future targeted therapies.” Dr. Aifantis is also a Howard Hughes Medical Institute Early Career Scientist.

The Notch signal path, the complex network of intracellular interactions that occurs after a protein called Notch is activated on the cell surface, is an actor well known in cancer, but the new study found that members of these different functions so unexpectedly to produce the disease. Notch is named after a particular type of mutation, first identified almost 100 years, which gives fruit flies notched wings.

This study was funded by the Howard Hughes Medical Institute.

Last year, acute myeloid leukemia was diagnosed in more than 12 000 adults and the disease is nearly 9,000 lives in the United States, according to the National Cancer Institute. The blood cancer is the most common type of acute leukemia in adults. Normally, the bone marrow produces blood stem cells (immature) that accumulate over time. Some of them are a form called myeloid and lymphoid others. The lymphoid stem cell develops into a white blood cell, while the most versatile myeloid stem cell develops into red blood cells, white cells and platelets, which prevents clotting. Cancer occurs when too many immature myeloid stem cells are produced in the blood and bone marrow.

The study is published in the May 12, 2011 issue of the journal Nature.