DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies
Identifieur interne : 001945 ( Ncbi/Merge ); précédent : 001944; suivant : 001946DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies
Auteurs : Ap Im [États-Unis] ; Ar Sehgal [États-Unis] ; Mp Carroll [États-Unis] ; Bd Smith [États-Unis] ; A. Tefferi [États-Unis] ; De Johnson [États-Unis] ; M. Boyiadzis [États-Unis]Source :
- Leukemia [ 0887-6924 ] ; 2014.
Descripteurs français
- KwdFr :
- DNA (cytosine-5-)-methyltransferase (génétique), Humains, Isocitrate dehydrogenases (génétique), Leucémie aigüe myéloïde (génétique), Leucémie aigüe myéloïde (traitement médicamenteux), Mutation, Pronostic, Protéines nucléaires (génétique), Syndromes myélodysplasiques (génétique), Syndromes myéloprolifératifs (génétique), Tyrosine kinase-3 de type fms (génétique).
- MESH :
- génétique : DNA (cytosine-5-)-methyltransferase, Isocitrate dehydrogenases, Leucémie aigüe myéloïde, Protéines nucléaires, Syndromes myélodysplasiques, Syndromes myéloprolifératifs, Tyrosine kinase-3 de type fms.
- traitement médicamenteux : Leucémie aigüe myéloïde.
- Humains, Mutation, Pronostic.
English descriptors
- KwdEn :
- DNA (Cytosine-5-)-Methyltransferase (genetics), Humans, Isocitrate Dehydrogenase (genetics), Leukemia, Myeloid, Acute (drug therapy), Leukemia, Myeloid, Acute (genetics), Mutation, Myelodysplastic Syndromes (genetics), Myeloproliferative Disorders (genetics), Nuclear Proteins (genetics), Prognosis, fms-Like Tyrosine Kinase 3 (genetics).
- MESH :
- chemical , genetics : DNA (Cytosine-5-)-Methyltransferase, Isocitrate Dehydrogenase, Nuclear Proteins, fms-Like Tyrosine Kinase 3.
- drug therapy : Leukemia, Myeloid, Acute.
- genetics : Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myeloproliferative Disorders.
- Humans, Mutation, Prognosis.
Abstract
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
Url:
DOI: 10.1038/leu.2014.124
PubMed: 24699305
PubMed Central: 4234093
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PMC:4234093Le document en format XML
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<series><title level="j">Leukemia</title>
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<term>Leukemia, Myeloid, Acute (drug therapy)</term>
<term>Leukemia, Myeloid, Acute (genetics)</term>
<term>Mutation</term>
<term>Myelodysplastic Syndromes (genetics)</term>
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<term>Leucémie aigüe myéloïde (traitement médicamenteux)</term>
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<term>Pronostic</term>
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<term>Syndromes myélodysplasiques (génétique)</term>
<term>Syndromes myéloprolifératifs (génétique)</term>
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<term>fms-Like Tyrosine Kinase 3</term>
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<term>Myeloproliferative Disorders</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">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 <italic>DNMT3A</italic>
, <italic>IDH1</italic>
or <italic>IDH2</italic>
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.</p>
</div>
</front>
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mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies</title>
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<series><title level="j">Leukemia</title>
<idno type="ISSN">0887-6924</idno>
<idno type="eISSN">1476-5551</idno>
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<front><div type="abstract" xml:lang="en"><p id="P1">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 <italic>DNMT3A</italic>
, <italic>IDH1</italic>
or <italic>IDH2</italic>
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.</p>
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<author><name sortKey="Boyiadzis, M" sort="Boyiadzis, M" uniqKey="Boyiadzis M" first="M" last="Boyiadzis">M. Boyiadzis</name>
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<term>Leukemia, Myeloid, Acute (drug therapy)</term>
<term>Leukemia, Myeloid, Acute (genetics)</term>
<term>Mutation</term>
<term>Myelodysplastic Syndromes (genetics)</term>
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<term>Tyrosine kinase-3 de type fms (génétique)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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