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Scientists identify crucial gene for blood development

BOSTON Researchers at Dana-Farber Cancer Institute have pinpointed a crucial gene on which the normal development of the body's entire blood system depends. If the gene is absent, even the most basic blood stem cells cannot be generated. In a mutated form, this gene can cause a rare and devastating form of leukemia.

Called MLL, the gene makes a protein that regulates the activity of a number of other genes involved in proper development of tissues and organs during embryonic life. The experimental results being published in the March 16 issue of Developmental Cell demonstrate that MLL is necessary for the development of the "master" stem cells that generate all the mature blood cells.

The team led by Patricia Ernst, PhD, and Stanley Korsmeyer, MD, reports that the discovery of the gene's critical role should help unveil important mechanisms in how the blood system develops, and could lead to ways of manipulating it in normal and cancerous conditions.

"The MLL gene, which is required to make all blood cells, is also a cause of a distinct human leukemia, suggesting that the blood's earliest stem cells are involved in this cancer," explains Korsmeyer, who is the director of Program in Molecular Oncology at Dana-Farber and a Howard Hughes Medical Investigator.

MLL stands for "mixed lineage leukemia," an aggressive, often fatal type of blood cancer that affects a small number of infants and some adults who have relapsed following treatment for leukemia. Dana-Farber researchers identified this rare cancer in 2002 on the basis of its genetic profile a specific pattern of gene activity in the cancer cells. It is caused by a mutation, or damage, in the MLL gene that results when the chromosome on which it resides breaks apart at that location. This chromosomal mishap leaves the MLL gene stuck in the "on" position so that white blood cells are overproduced, resulting in leukemia.

Scientists have previously found that chromosome breaks can damage o
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Contact: Janet Haley Dubow
janet_haley@dfci.harvard.edu
617-632-5665
Dana-Farber Cancer Institute
15-Mar-2004


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