Association Analysis Between Oncogenic Genes and the Efficacy of Demethylation Drug

Objectives:

In the present study, we investigated the relation between genetic mutations and complete remission (CR) in 78 leukemia patients treated with demethylation drug.

Methods:

One hundred and eleven leukemia-related genes were sequenced by ultra-deep targeted sequencing. Among these, 52 genes were found to be mutated, such as DNMT3A, TET2, IDH1, IDH2, etc., hotspot genes of demethylation drug treatment.

Results:

No DNMT3A nor TET2 mutations were found in 17 patients without significant remission after demethylation drug treatment, while 18% (11/61) patients with complete remission after demethylation drug treatment harbored DNMT3A mutations, and 10% (6/61) patients achieving complete remission after demethylation drug treatment harbored TET2mutations. The difference was statistically significant when compared with non-mutant group (P<0.05).

Conclusions:

Our study indicated a significant association between mutations of DNMT3A and TET2 and efficacyof demethylation drug-treated leukemia patients. Complete remission after demethylation drug treatment was achieved more frequently in the cohort harboring mutated DNMT3A or TET2, which is consistent with previous studies. Our findings suggest ultra-deep targeted sequencing is helpful for investigating the relation between mutated genes and the efficacy of drug. Moreover, it could be a way for screening more suitable patients for demethylation drug treatment in consideration of its extremely high expense.