Related Papers
Genes
What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort
2021 •
Eigil Kjeldsen
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 in...
Blood
Screening of novel genetic aberrations in pediatric acute myeloid leukemia: a report from the AIEOP AML-2002 study group
2012 •
E. Manara, Martina Pigazzi
Einstein (São Paulo)
Molecular and cytogenetic abnormalities in acute myeloid leukemia: review and case studies
2011 •
Roberta Sitnik
Postępy Higieny i Medycyny Doświadczalnej
Genetic basis of acute myeloid leukemia (AML): The most common molecular changes in patients with normal karyotype
Alicja Bartoszewska-Kubiak
Acute myeloid leukemia (AML) is a clonal disorder that results from errors in proliferation and differentiation of bone marrow stem cells from myeloid lineage. According to the Gilliland “two-hit” model, genes of both groups related to proliferation (e.g., FLT3) and differentiation (e.g., CEBPA) must be mutated for full development of AML. The genetic background of AML is very complicated and varied, from single nucleotide mutations or changes in gene expression to cytogenetic aberrations. The DNA sequencing results enable identification of important gene alterations that occur first and may lead the whole leukemogenesis (driver mutations). Some of them have prognostic significance – that is, they are related to the overall survival (OS), complete remission rate, and event-free survival (EFS). The most common molecular changes in AML are mutations in NPM1, CEBPA, FLT3, and DNMT3A. Alterations in NPM1 gene are associated with a good prognosis but simultaneous mutation in FLT3 may cha...
Molecular Biology
Mutational Profiling of Pediatric Myeloid Leukemia Subtypes without Clinically Significant Chromosomal Aberrations
2019 •
Olga V Muravenko
Supplementary Tables and Figures from Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators
2023 •
Maarten Fornerod
Haematologica
Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children’s Oncology Group protocol AAML0531
Michael Loken
Leukemia
Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia
2005 •
Ursula Creutzig
Cancer research
Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse
2016 •
Alan Gamis
The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML. One hundred forty-five somatic variants at diagnosis (median 6 mutations per patient) and 149 variants at relapse (median 6.5 mutations) were identified and verified by orthogonal methodologies. Recurrent somatic variants (in {greater than or equal to}2 patients) were identified for 10 genes (FLT3, NRAS, PTPN11, WT1, TET2, DHX15, DHX30, KIT, ETV6, KRAS), with variable persistence at relapse. The variant allele fraction (...
International journal of hematology
Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study
2018 •
Akiko Saito
Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine kinase 3 (AML) is associated with poor prognosis. We evaluated the results of the AML-05 study, in which all AMLpatients were assigned to receive hematopoietic stem cell transplantation (HSCT) in the first remission (1CR). We also investigated the effects of additional genetic alterations on FLT3-ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among the 47 AMLpatients were 42.2 and 36.8%, respectively. The 5-year disease-free survival rate among 29 patients without induction failure was 58.4%. We defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations survived, while seven of eight patients who expressed the NUP98-NSD1 chimera failed to achieve 1CR and died. Multivariate analysis revealed that AR >...
