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Background    DNMT3A  mutations are frequently discovered in acute myeloid leukemia (AML), associated with poor outcome. Recently, a relapse case report of AML extramedullary disease has showed that AML cells harboring  DNMT3A  variation were detected in the cerebral spinal fluid. However, whether a causal relationship exists between  DNMT3A  mutation (D3Amut) and extramedullary infiltration (EMI) is unclear.    Methods  We took advantage of  DNMT3A  (R882C) mutation-carrying AML cell strain, that is, OCI-AML3, assessing its migration ability in vitro and in vivo. By RNA interfering technology and a xenograft mouse model, we evaluated the effect of  DNMT3A  mutation on cell mobility and explored the possible mechanism.    Results  OCI-AML3 displayed extraordinary migration ability in vitro and infiltrated into meninges of NOD/SCID mice after intravenous transfusion. We found that this leukemic migration or infiltration capacity was significantly compromised by the knockdown of DNMT3A mutant. Notably, TWIST1, a critical inducer of epithelial–mesenchymal transition, which underlies the metastasis of carcinomas, was highly expressed in association with R882 mutations. Abrogation of TWIST1 in  DNMT3A  mutated cells considerably weakened their mobility or infiltration.    Conclusions  Our results demonstrate that D3Amut in OCI-AML3 strain enhances leukemic aggressiveness by promoting EMI process, which is partially through upregulating TWIST1.    Electronic supplementary material  The online version of this article (doi:10.1186/s13045-016-0337-3) contains supplementary material, which is available to authorized users.

DNMT3A mutation leads to leukemic extramedullary infiltration mediated by TWIST1