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Newswise NEW YORK, NY (January 21, 2014) Acute myeloid leukemia (AML) is a blood cancer, but for many patients the cancer may originate from an unusual source: a mutation in their bone cells.

In a study published today in the online edition of Nature, researchers at Columbia University Medical Center (CUMC) found that a mutation in the bone cells called osteoblasts, which build new bone, causes AML in mice. The mutation was found in nearly 40 percent of patients with AML or myelodysplastic syndrome (MDS), a precursor condition, who were examined as part of the study.

The researchers were able to stop production of leukemic blood cells in the mice with a drug that blocked the effects of the osteoblast mutation, suggesting that a similar drug may benefit a large portion of AML and MDS patients.

If the mutation works the same way in humans, our study suggests practical ways that we may be able to intervene with a drug or an antibody. It may give us a tool for a disease that is rarely curable, said the studys lead investigator Stavroula Kousteni, PhD, associate professor of medical sciences in medicine and physiology & cellular biophysics at CUMC.

This paper goes to the heart of bi-directional translational research, as it represents collaboration between institutions, as well as between clinicians and basic scientists, said Azra Raza, MD, director of CUMCs MDS Center and a co-author of the study. The Kousteni Lab made the observation that a mutation affecting b-catenin in the bone marrow microenvironment cells of mice can cause leukemia. Clinicians from Memorial Sloan-Kettering and CUMC then extracted bone marrow samples of patients with MDS and AML from their tissue repositories, to confirm a similar pathway in a subset of patients. This incredibly important observation opens the possibilities of novel therapies for these dreaded diseases using non-chemotherapeutic approaches.

AML is one of the most common types of leukemia in adults, with about 15,000 cases diagnosed in the U.S. each year. The disease progresses rapidly, and only about 25 percent survive three years after diagnosis. MDS is a group of blood disorders diagnosed in about 10,000 people in the U.S. each year. Many people with MDS eventually develop AML.

Mutation of beta-catenin gene in osteoblasts causes AML in mice

In the current study, Dr. Kousteni and colleagues investigated a mouse strain that dies soon after birth from severe blood abnormalities. They found that the disease, which was the same as AML, was caused by a mutation in the beta-catenin gene in the animals osteoblasts.

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Common Blood Cancer May Be Initiated by Single Mutation in Bone Cells

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