What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort
Normal karyotype acute myeloid leukemia (NK-AML) constitutes 20–25% of pediatric AML and detailed molecular analysis is essential to unravel the genetic background of this group. Using publicly available sequencing data from the TARGET-AML initiative, we investigated the mutational landscape of NK-A...
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MDPI AG
2021-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/6/792 |
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| author | Morten Krogh Herlin Sara A. Yones Eigil Kjeldsen Linda Holmfeldt Henrik Hasle |
| author_facet | Morten Krogh Herlin Sara A. Yones Eigil Kjeldsen Linda Holmfeldt Henrik Hasle |
| author_sort | Morten Krogh Herlin |
| collection | DOAJ |
| description | Normal karyotype acute myeloid leukemia (NK-AML) constitutes 20–25% of pediatric AML and detailed molecular analysis is essential to unravel the genetic background of this group. Using publicly available sequencing data from the TARGET-AML initiative, we investigated the mutational landscape of NK-AML in comparison with abnormal karyotype AML (AK-AML). In 164 (97.6%) of 168 independent NK-AML samples, at least one somatic protein-coding mutation was identified using whole-genome or targeted capture sequencing. We identified a unique mutational landscape of NK-AML characterized by a higher prevalence of mutated <i>CEBPA</i>, <i>FLT3</i>, <i>GATA2</i>, <i>NPM1</i>, <i>PTPN11</i>, <i>TET2</i>, and <i>WT1</i> and a lower prevalence of mutated <i>KIT</i>, <i>KRAS</i>, and <i>NRAS</i> compared with AK-AML. Mutated <i>CEBPA</i> often co-occurred with mutated <i>GATA2</i>, whereas mutated <i>FLT3</i> co-occurred with mutated <i>WT1</i> and <i>NPM1</i>. In multivariate regression analysis, we identified younger age, WBC count ≥50 × 10<sup>9</sup>/L, <i>FLT3</i>-internal tandem duplications, and mutated <i>WT1</i> as independent predictors of adverse prognosis and mutated <i>NPM1</i> and <i>GATA2</i> as independent predictors of favorable prognosis in NK-AML. In conclusion, NK-AML in children is characterized by a unique mutational landscape which impacts the disease outcome. |
| first_indexed | 2024-03-10T11:10:39Z |
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| language | English |
| last_indexed | 2024-03-10T11:10:39Z |
| publishDate | 2021-05-01 |
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| series | Genes |
| spelling | doaj.art-c7227feb18fb43d8a5c6de0733f081a32023-11-21T20:52:06ZengMDPI AGGenes2073-44252021-05-0112679210.3390/genes12060792What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML CohortMorten Krogh Herlin0Sara A. Yones1Eigil Kjeldsen2Linda Holmfeldt3Henrik Hasle4Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, 8200 Aarhus N, DenmarkScience for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, 75185 Uppsala, SwedenDepartment of Hematology, Aarhus University Hospital, 8200 Aarhus N, DenmarkDepartment of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 75185 Uppsala, SwedenDepartment of Pediatrics and Adolescent Medicine, Aarhus University Hospital, 8200 Aarhus N, DenmarkNormal karyotype acute myeloid leukemia (NK-AML) constitutes 20–25% of pediatric AML and detailed molecular analysis is essential to unravel the genetic background of this group. Using publicly available sequencing data from the TARGET-AML initiative, we investigated the mutational landscape of NK-AML in comparison with abnormal karyotype AML (AK-AML). In 164 (97.6%) of 168 independent NK-AML samples, at least one somatic protein-coding mutation was identified using whole-genome or targeted capture sequencing. We identified a unique mutational landscape of NK-AML characterized by a higher prevalence of mutated <i>CEBPA</i>, <i>FLT3</i>, <i>GATA2</i>, <i>NPM1</i>, <i>PTPN11</i>, <i>TET2</i>, and <i>WT1</i> and a lower prevalence of mutated <i>KIT</i>, <i>KRAS</i>, and <i>NRAS</i> compared with AK-AML. Mutated <i>CEBPA</i> often co-occurred with mutated <i>GATA2</i>, whereas mutated <i>FLT3</i> co-occurred with mutated <i>WT1</i> and <i>NPM1</i>. In multivariate regression analysis, we identified younger age, WBC count ≥50 × 10<sup>9</sup>/L, <i>FLT3</i>-internal tandem duplications, and mutated <i>WT1</i> as independent predictors of adverse prognosis and mutated <i>NPM1</i> and <i>GATA2</i> as independent predictors of favorable prognosis in NK-AML. In conclusion, NK-AML in children is characterized by a unique mutational landscape which impacts the disease outcome.https://www.mdpi.com/2073-4425/12/6/792pediatric acute myeloid leukemianormal karyotypecytogenetically normalmutational landscapemolecular geneticscytogenetics |
| spellingShingle | Morten Krogh Herlin Sara A. Yones Eigil Kjeldsen Linda Holmfeldt Henrik Hasle What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort Genes pediatric acute myeloid leukemia normal karyotype cytogenetically normal mutational landscape molecular genetics cytogenetics |
| title | What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort |
| title_full | What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort |
| title_fullStr | What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort |
| title_full_unstemmed | What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort |
| title_short | What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort |
| title_sort | what is abnormal in normal karyotype acute myeloid leukemia in children analysis of the mutational landscape and prognosis of the target aml cohort |
| topic | pediatric acute myeloid leukemia normal karyotype cytogenetically normal mutational landscape molecular genetics cytogenetics |
| url | https://www.mdpi.com/2073-4425/12/6/792 |
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