DNMT3A mutation leads to leukemic extramedullary infiltration mediated by TWIST1.
J Hematol Oncol
; 9(1): 106, 2016 10 10.
Article
em En
| MEDLINE
| ID: mdl-27724883
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Leucemia Mieloide Aguda
/
DNA (Citosina-5-)-Metiltransferases
/
Proteína 1 Relacionada a Twist
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Hematol Oncol
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China