DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies.

Im, A P; Sehgal, A R; Carroll, M P; Smith, B D; Tefferi, A; Johnson, D E; Boyiadzis, M

Im, A P; Sehgal, A R; Carroll, M P; Smith, B D; Tefferi, A; Johnson, D E; Boyiadzis, M.

Afiliación

Im AP; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Sehgal AR; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Carroll MP; Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Smith BD; The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology at the Johns Hopkins University, Baltimore, MD, USA.
Tefferi A; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Johnson DE; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Boyiadzis M; Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.

Leukemia ; 28(9): 1774-83, 2014 Sep.

Article en En | MEDLINE | ID: mdl-24699305

RESUMEN

The development of effective treatment strategies for most forms of acute myeloid leukemia (AML) has languished for the past several decades. There are a number of reasons for this, but key among them is the considerable heterogeneity of this disease and the paucity of molecular markers that can be used to predict clinical outcomes and responsiveness to different therapies. The recent large-scale sequencing of AML genomes is now providing opportunities for patient stratification and personalized approaches to treatment that are based on individual mutational profiles. It is particularly notable that studies by The Cancer Genome Atlas and others have determined that 44% of patients with AML exhibit mutations in genes that regulate methylation of genomic DNA. In particular, frequent mutation has been observed in the genes encoding DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2), as well as Tet oncogene family member 2. This review will summarize the incidence of these mutations, their impact on biochemical functions including epigenetic modification of genomic DNA and their potential usefulness as prognostic indicators. Importantly, the presence of DNMT3A, IDH1 or IDH2 mutations may confer sensitivity to novel therapeutic approaches, including the use of demethylating agents. Therefore, the clinical experience with decitabine and azacitidine in the treatment of patients harboring these mutations will be reviewed. Overall, we propose that understanding the role of these mutations in AML biology will lead to more rational therapeutic approaches targeting molecularly defined subtypes of the disease.

Asunto(s)

ADN (Citosina-5-)-Metiltransferasas/genética; Isocitrato Deshidrogenasa/genética; Leucemia Mieloide Aguda/genética; Mutación; ADN Metiltransferasa 3A; Humanos; Leucemia Mieloide Aguda/tratamiento farmacológico; Síndromes Mielodisplásicos/genética; Trastornos Mieloproliferativos/genética; Proteínas Nucleares/genética; Nucleofosmina; Pronóstico; Tirosina Quinasa 3 Similar a fms/genética

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / ADN (Citosina-5-)-Metiltransferasas / Isocitrato Deshidrogenasa / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google