Mutation identified in drug resistant childhood leukemia
Nature Genetics
2013년2월4일
Mutations in the cytosolic 5’-nucleotidase II (NT5C2) gene that contribute to chemotherapy resistance in children with acute lymphoblastic leukemia (ALL) are reported in a study published online this week in Nature Genetics.
ALL is the most common pediatric malignancy, accounting for greater than 25% of all childhood cancers. Cure rates are high, but 10-20% of patients experience disease recurrence. Relapsed childhood ALL carries a poor prognosis due to intrinsic drug resistance, though the biological pathways that mediate this resistance are unknown.
William Carroll and colleagues report on transcriptome RNA sequencing of matched bone marrow samples obtained at diagnosis and relapse from ten ALL patients. They identified relapse specific mutations in NT5C2 in two patients, as well as five additional NT5C2 mutations in 61 additional relapse specimens. The authors found that mutant NT5C2 proteins had increased enzymatic activity and conferred resistance to cultured cells treated with nucleoside analogue therapies.
doi: 10.1038/ng.2558
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