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St. Jude Discovery Offers New Avenues to Understanding an Aggressive Form of Leukemia
Date:4/14/2008

ranslocation 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 expression," Downing said.

In their new study, the researchers re-examined the genetic makeup of 304 ALL patients who had been studied earlier. The group included 43 pediatric and adult BCR-ABL1 ALL patients and 23 adults with CML. Using a more sensitive technology, the scientists increased the number of genetic mutations found in their original gene survey.

In the first study, the gene most commonly altered was one called PAX5, followed by a gene designated IKZF1. Its protein, Ikaros, is involved in the development and differentiation of B lymphocyte cells, which are part of the immune system.

"The vast majority of pediatric acute lymphoblastic leukemias are of B-cell lineage," Downing said.

Among the ALL patients, the researchers found an average of 8.79 copy number alterations, a form of genetic change linked to the development and progression of cancer. The most common change was deletion of the gene for Ikaros.

The gene was deleted in 36 (83.7 percent) of the BCR-ABL1 ALL patients, including 76.2 percent of the pediatric and 90.9 percent of the adult cases.

"The loss of the Ikaros gene is a nearly obligatory lesion for the development of BCR-ABL1 ALL," Downing said, "and clearly must be a genetic lesion that is cooperating with BCR-ABL1."

Moreover, a gene known as CDKN2A was deleted in 53.5 percent of the BCR-ABL1 ALL patients, 87.5 percent of whom also had lost the gene for Ikaros. The PAX5 deletion occurred in 51 percent of the BCR-ABL1 ALL patients; and 95 percent of these people were missing the Ikaros gene.

Among the CML patients whose disease converted to ALL, two out of three had the deletion of the Ikaros gene; a lower percentage of those who converted to acute myeloblastic leuke
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SOURCE St. Jude Children's Research Hospital
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