Low frequency of DNMT3A mutations in pediatric AML, and the identification of the OCI-AML3 cell line as an in vitro model

Hollink, Iris H.I.M.; Feng, Qiang; Oorschot, Astrid A Danen-van; Arentsen-Peters, Susan T.C.J.M.; Verboon, Lonneke; Zhang, P; Haas, Valérie de; Reinhardt, Dirk; Creutzig, Ursula; Trka, Jan; Pieters, Rob; Heuvel‐Eibrink, Marry M. van den; Wang, J; Zwaan, C. Michel

doi:10.1038/leu.2011.210

Cited by 37 publications

(24 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21,22 In this study of 206 pediatric patients with de novo AML, we systematically analyzed known mutated genes, examined more patients and genes than we have reported previously, 23 and included 5 recently identified genes that encode epigenetic modifiers. We also The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%

“…19 DNMT3A mutations have been rare in pediatric patients with AML: in one study that included 180 cases, no patients were found, 20 and only 1.0% and 2.1% of the patients in the other two studies were reported. 21,22 In this study of 206 pediatric patients with de novo AML, we systematically analyzed known mutated genes, examined more patients and genes than we have reported previously, 23 and included 5 recently identified genes that encode epigenetic modifiers. We also The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A

Liang

Liu

Yang

et al. 2013

Blood

View full text Add to dashboard Cite

Key Points• A comprehensive study of 19 gene mutations and their cooperation, including the first report of ASXL1 and TET2 mutations in pediatric AML.• The development of pediatric AML requires fewer gene mutations than adult AML.Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with polymerase chain reaction2 based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III, and 5.6% class IV. FLT3-internal tandem duplication was most frequent, and 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-partial tandem duplication. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2, and IDH1 mutations were associated with specific genetic subtypes. (Blood. 2013;121(15):2988-2995 IntroductionComprehensive analyses in de novo childhood acute myeloid leukemia (AML) of gene mutations involving epigenetic regulators have been limited. The ASXL1 (additional sex comb-like 1) gene mapping to chromosome 20q acts as a cofactor of retinoic acid receptor via binding to steroid receptor coactivation-1 and belongs to enhancer of trithorax and polycomb genes that can both activate and repress the HOX gene.1,2 Very recently, it has been demonstrated that ASXL1 loss-of-function mutations result in the loss of polycomb repressive complex 22mediated histone H3 lysine 27 trimethylation, which promotes myeloid leukemia transformation.3 ASXL1 mutations conferred a poor outcome in adult AML, 4,5 but there have been no reports of ASXL1 mutations in childhood AML. TET proteins encode a-ketoglutarate-dependent oxygenases, which are involved in the conversion of 5-methylcytosine to 5-hydroxymethylcytosine. 6 TET2 protein is important for normal myelopoiesis, and disruption of TET2 enzymatic activity results in altered DNA methylation and favors myeloid neoplasm transformation.7 IDH1 and IDH2 mutations convert a-ketoglutarate to 2-hydroxyglutarate, which disrupts TET2 function. 8,9 Somatic mutations of TET2 were identified with microdeletion at 4q24 in myeloid neoplasms by the use of high-resolution single-nucleotide polymorphism microarrays.10,11 TET2 mutations were detected in adult AML with a frequency ranging from 7% to 23%, but t...

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A

Liang

Liu

Yang

et al. 2013

Blood

View full text Add to dashboard Cite

show abstract

“…Most of these studies focused on the relevance of mutations in a single gene and mutations were detected in 1-4% of the patients. [9][10][11][12][13] Although no significant statements can be made since study cohorts were quite heterogeneous, most mutations seemed to occur in cytogenetically normal (CN) AML, a subgroup that comprises 20-25% of all pediatric AML. This distribution corresponds to adult AML data in which most epigenetic regulator gene mutations were also identified in CN patients.…”

Section: 8mentioning

confidence: 99%

Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia

et al. 2014

View full text Add to dashboard Cite

show abstract

“…180,181 Similarly, the DMNT3A mutation is found at a higher percentage in adult (15%-20%) compared to childhood (2%) AML. 63,182,183 The FLT3-ITD mutation is found in 25% of adult and 15% of childhood AML. 43,184 Two less well-studied mutations that may serve as MRD markers include CEBPA and MLLpartial tandem duplications.…”

Section: Rq-pcrmentioning

confidence: 99%

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Mizutani

Hara

Fujita

et al. 2016

Bone Marrow Transplant

View full text Add to dashboard Cite

Low frequency of DNMT3A mutations in pediatric AML, and the identification of the OCI-AML3 cell line as an in vitro model

Cited by 37 publications

References 9 publications

Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A

Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A

Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Contact Info

Product

Resources

About