DNMT3A mutations and prognostic significance in childhood acute lymphoblastic leukemia

Abstract

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.

Keywords::

• DNMT3A
• mutations
• childhood acute lymphoblastic leukemia
• MRD
• prognosis

Acknowledgements

This work was supported in part by a grant-in-aid from a project of the Beijing Municipal Commission of Education (No. KZ201410025021); Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding support (No. ZY201404); the Beijing Health Qualified Personnel Program (No. 2011-3-049), National Science & Technology Major Project of the 12th 5-Year Plan (No. 2011ZX09302-007-01), the National Key Technologies Research & Development Program of the 11th 5-Year Plan (No. 2007BAI04B03), Beijing Municipal Science & Technology Project (No. D0905001040431) and Beijing Novel Program (No. 2005B06). We thank Quangeng Zhang and Zhigang Li for study design; Chao Gao, Lei Cui, Shuguang Liu and Xiaoxi Zhao for sample collection and some data analysis; Minyuan Wu and Ruidong Zhang for providing the clinical data and therapy program; Guoren Deng for preparation of the manuscript; and our patients.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.