Research press release


Nature Genetics

Mutation identified in drug resistant childhood leukemia



今回、W Carrollたちは、同じALL患者から診断時と再発時に得た骨髄試料を10人分集め、RNA塩基配列解読(RNA-seq)を行った。その結果、2人の患者においてNT5C2遺伝子の再発特異的変異が同定され、さらに、61の再発試料でNT5C2遺伝子の変異が5つ同定された。また、Carrollたちは、変異型NT5C2タンパク質の酵素活性が亢進しており、ヌクレオシド類似体療法を行った培養細胞が耐性を獲得したことも明らかにした。

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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