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Tracing the Origins of Leukemia

Caption: Hairy cell leukemia is a rare blood cancer composed of hallmark leukemic cells that are unlike any known normal cell in the human body. It has long been assumed that hairy cell leukemia arises due to mutations acquired by normal, mature B lymphocytes (shown on left). However, the actual cell of origin of this disorder has been never been well understood. Recently, it was discovered that hairy cell leukemia cells contain a mutation in an important gene, BRAFV, which results in activation of the BRAF molecule, promoting cell growth and survival. By tracing the presence of this mutation in blood stem and progenitor cells we have determined that the BRAF mutation (BRAFV600E) actually originates in a small proportion of the blood stem and progenitor cells in hairy cell leukemia patients, and therefore it is likely that this mutation occurs early in the development of disease. The functional consequence of this mutation in blood stem cells is the preferential development of abnormal B lymphocytes, which predisposes patients to subsequently develop hairy cell leukemia (shown on right). This finding challenges our traditional view of the events leading to the development of the disease and has broad implications for the way to diagnose, treat, and even prevent, disease. This image relates to a paper that appeared in the May 28, 2014, issue of Science Translational Medicine, published by AAAS. The paper, by Dr. S.S. Chung at Memorial Sloan Kettering Cancer Center in New York, N.Y., and colleagues was titled, "Hematopoietic Stem Cell Origin of BRAFV600E Mutations in Hairy Cell Leukemia."

Credit: Omar Abdel-Wahab

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