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St. Jude discovery offers new avenues to understanding an aggressive form of leukemia
Date:4/14/2008

Researchers at St. Jude Childrens Research Hospital have discovered evidence that a series of genetic mutations work together to initiate most cases of an aggressive and often-fatal form of acute lymphoblastic leukemia (ALL).

These defects, known as "cooperating oncogenic lesions," include the deletion of a gene, IKZF1, whose protein, Ikaros, normally helps guide the development of a blood stem cell into a lymphocyte. The researchers also found that loss of the same gene accompanied the transformation of chronic myelogenous leukemias (CMLs) to a life-threatening acute stage.

"These findings provide new avenues to pursue to gain a better understanding of these disease processes and, ultimately, to develop better therapies," said James R. Downing, M.D., St. Jude scientific director and chair of the Department of Pathology.

The new study, which he and his colleagues reported in the advance online publication of the journal "Nature," adds further support to a key concept in cancer genetics: Malignancies frequently require mutations in multiple genes in order to develop.

Cells contain oncogenes, which exist harmlessly until something triggers them to turn the cells malignant.

"It really takes a series of genetic lesions to lead to cancer," Downing said. "You may get activation of an oncogene, but you may also need activation of a tumor suppressor gene and an alteration in a cell-death pathway."

St. Jude researchers sought to identify genetic differences between CML and a form of acute leukemia known as BCR-ABL1{positive ALL.

Both diseases are characterized by the Philadelphia chromosome, which results from the translocation (joining) of parts of two different chromosomes. The result of this translocation is the expression of BCR-ABL1, an oncogene.

"It appears from our study, and other work published previously, that all you need to get CML is that chromosomal translocation and BCR-ABL1 expre
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Contact: Carrie Strehlau
media@stjude.org
901-495-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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