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Mar 07, 2013
 |  BC Innovations  |  Targets & Mechanisms

ALL emerges from relapse

Separate teams led by researchers from New York University and Columbia University have identified mutations in 5ʹ-nucleotidase cytosolic II that predict relapse, drug resistance and poor prognosis in acute lymphoblastic leukemia.1,2 Inhibiting the enzyme could improve disease outcomes and sensitize some relapsed patients to marketed acute lymphoblastic leukemia therapies.

Current treatment regimens for ALL involve first-line chemotherapy followed by maintenance therapy that includes the purine analogs 6-mercaptopurine (6-MP) and 6-tioguanine (6-TG).

Although the treatments are effective for many patients, about 10%-20% of pediatric patients and up to 50% of adult patients relapse. The relapsed disease often is resistant to drugs and has a cure rate of less than 40%.3

The two teams conducted genetic studies on patient samples to find the underlying mechanisms of ALL relapse. Both converged on overlapping sets of gain-of-function mutations in 5ʹ-nucleotidase cytosolic II (NT5C2), which were associated with disease relapse and could be causing drug resistance.

In a paper published in Nature Genetics, William Carroll and colleagues at NYU sequenced RNA samples from pediatric patients with B lymphoblastic leukemia, the most common form of ALL. Carroll is a professor of pediatrics and director of the NYU Cancer Institute.

The team found 20 missense mutations in samples from 10 relapse patients that were absent in matched samples from patients at diagnosis or during remission, including two mutations in the coding region of NT5C2.

In a follow-up analysis of samples from another 61 relapse patients, full exon sequencing...

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