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New Gene Findings Will Help Guide Treatment in Infant Leukemia
Date:12/5/2009

region, called a translocation, leads to the production of a fusion gene and an abnormal protein and, ultimately, to leukemia.

The current study covered 221 infants with ALL in a COG clinical trial. Researchers detected MLL translocations in the ALL cells of 74 percent of the patients. The two most common partner genes that fused with the MLL gene were AF4 on chromosome 4 and ENL on chromosome 19. Both of these translocations were associated with a very poor prognosis; event-free survival (EFS) rates were 34 percent with AF4 and 29 percent with ENL, compared to the overall EFS rate of 46 percent among all infants in the study--still far inferior to survival rates that are seen in children above age one.

The EFS rates with these two partner genes were even lower when the infants were less than 90 days old at diagnosis. Conversely, the survival rates were better when these partner genes fused to MLL in the leukemia cells of older infants. Though age was already known to be a classic prognostic factor in infant ALL, the differences in survival in younger versus older babies when these specific partner genes are involved had not been so clear.

In contrast, outcomes were better for infants with ALL when the third most common partner gene, AF9, fused to MLL, or when the MLL gene was unaffected. In these patients, the respective EFS rates were 68 and 66 percent. The researchers also analyzed white blood cell counts (WBC)--another classic prognostic factor in leukemia. They found that when MLL was fused to AF4, the infants were far more likely to have higher WBC, while the WBC was lower when MLL fused to AF9.

More refined knowledge of how the different partner genes of MLL in infant ALL are connected to the underlying molecular biology of the disease may guide the researchers to more appropriate treatment decisions. "Our abili
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SOURCE The Children's Hospital of Philadelphia
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