What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort

Genes

Eigil Kjeldsen¹  Linda Holmfeldt²  Henrik Hasle³  MortenKrogh Herlin³  SaraA. Yones⁴ 

[1] Department of Hematology, Aarhus University Hospital, 8200 Aarhus N, Denmark;Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 75185 Uppsala, Sweden;Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark;Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, 75185 Uppsala, Sweden;

关键词: pediatric acute myeloid leukemia;    normal karyotype;    cytogenetically normal;    mutational landscape;    molecular genetics;    cytogenetics;   

DOI  :  10.3390/genes12060792

来源: DOAJ

【 摘 要 】

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 CEBPA, FLT3, GATA2, NPM1, PTPN11, TET2, and WT1 and a lower prevalence of mutated KIT, KRAS, and NRAS compared with AK-AML. Mutated CEBPA often co-occurred with mutated GATA2, whereas mutated FLT3 co-occurred with mutated WT1 and NPM1. In multivariate regression analysis, we identified younger age, WBC count ≥50 × 10⁹/L, FLT3-internal tandem duplications, and mutated WT1 as independent predictors of adverse prognosis and mutated NPM1 and GATA2 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.

【 授权许可】

Unknown