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    Gerard C. Grosveld, PhD

    Gerard C. Grosveld, PhD



    Fusion gene can cause leukemia

    A mutation caused by the fusion of two genes makes mice vulnerable to the cancer-causing effects of a second cancer-causing event, according to a team of St. Jude researchers. The investigators showed that this so-called fusion protein, MN1-TEL, makes certain white blood cells become leukemic if the cells undergo another cancer-causing “hit.”

    The finding is a major advancement in helping researchers define the specific steps that cause this cancer, according to Gerard Grosveld, PhD, chair of Genetics and Tumor Cell Biology. Grosveld is lead author of two reports on this work that appear in the August 4 and 16 issues of Blood.

    MN1-TEL is the product of a chromosome translocation, t(12;22)(p12;q12), in human myeloid malignancies. Translocations occur when one gene—or a part of one gene—moves from its normal place on a chromosome and fuses with a gene elsewhere.

    “MN1-TEL puts hematopoietic cells under stress, and this stress provokes other oncogenic events that together with MN1-TEL cause leukemia,” said Grosveld.

    The researchers used Aml1 regulatory sequences to express the MN1-TEL fusion protein in blood stem cells in order to study its ability to cause leukemia in different types of hematopoietic cells (blood stem cells give rise to populations of different types of blood cells). Regulatory sequences are pieces of DNA that prompt a specific nearby gene to be expressed.

    Although MN1-TEL causes only myeloid leukemia in humans because its expression is restricted to myeloid cells, the team showed that MN1-TEL has a broader oncogenic potential: it can cause both myeloid and lymphoid leukemia.

    Myeloid leukemia occurs in white blood cells called monocytes and granulocytes; lymphoid leukemia occurs in white cells called lymphocytes. While MN1-TEL drives the leukemic process, the difference in leukemia outcome in the mice is entirely determined by the nature of the secondary oncogenic step.

     

    Last update: October 2005