DNMT3A mutations and prognostic significance in childhood acute lymphoblastic leukemia.

Little is known about DNMT3A mutations in childhood acute lymphoblastic leukemia (ALL). We screened for DNMT3A mutations in exon 23 and its adjacent intron regions in diagnostic samples of 201 children with ALL. The cDNA samples from 82 patients were also sequenced to identify other mutations in the entire coding region. DNMT3A mutations were detected in exon 23 and its adjacent intron regions only in five patients (2.5%). There was only one mutation in exon 23 in two patients, respectively. In the other three patients, five intronic mutations were found. None of the mutations was found in the five corresponding complete remission samples. DNMT3A mutations were correlated with higher minimal residual disease at the end of remission induction (p = 0.078). Treatment outcome was obviously worse in patients with DNMT3A mutations than in other patients (p < 0.05). Thus, DNMT3A mutations can be found in a few children with ALL, and may have an adverse impact on prognosis.

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