scholarly journals The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

2017 ◽  
Vol 24 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Hamid Bolouri ◽  
Jason E Farrar ◽  
Timothy Triche ◽  
Rhonda E Ries ◽  
Emilia L Lim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Pediatric Acute Myeloid Leukemia ◽  
Structural Alterations ◽  
Molecular Landscape ◽  
Acute Myeloid

scholarly journals The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

2017 ◽  
Author(s):  
Hamid Bolouri ◽  
Jason E. Farrar ◽  
Timothy Triche ◽  
Rhonda E. Ries ◽  
Emilia L. Lim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Dna Hypermethylation ◽  
Pediatric Acute Myeloid Leukemia ◽  
Mirna Sequencing ◽  
Promoter Dna ◽  
Pediatric Aml ◽  
Molecular Landscape ◽  
Acute Myeloid

AbstractWe present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Children’s Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, miRNA sequencing and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including novel gene fusions and focalMBNL1,ZEB2, andELF1deletions, were disproportionately prevalent in young as compared to adult patients. Conversely,DNMT3AandTP53mutations, common in adults, are conspicuously absent from virtually all pediatric cases. NovelGATA2,FLT3, andCBLmutations, recurrentMYC-ITD, NRAS, KRAS, andWT1mutations are frequent in pediatric AML. Deletions, mutations, and promoter DNA hypermethylation convergently impact Wnt signaling, Polycomb repression, innate immune cell interactions, and a cluster of zinc finger genes associated withKMT2Arearrangements. These results highlight the need for, and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.

scholarly journals NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia

2021 ◽  
Vol 22 (9) ◽  
pp. 4575
Author(s):  
Vincenza Barresi ◽  
Virginia Di Bella ◽  
Nellina Andriano ◽  
Anna Provvidenza Privitera ◽  
Paola Bonaccorso ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Integrated Analysis ◽  
Induction Phase ◽  
Pediatric Acute Myeloid Leukemia ◽  
Expression Arrays ◽  
Primary Induction ◽  
Induction Failure ◽  
Acute Myeloid

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

No Prognostic Impact of the WT1 Gene Single Nucleotide Polymorphism rs16754 in Pediatric Acute Myeloid Leukemia

2010 ◽  
Vol 28 (28) ◽  
pp. e523-e526 ◽  
Author(s):  
Iris H.I.M. Hollink ◽  
Marry M. van den Heuvel-Eibrink ◽  
Martin Zimmermann ◽  
Brian V. Balgobind ◽  
Susan T.C.J.M. Arentsen-Peters ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Impact ◽  
Wt1 Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pediatric Acute Myeloid Leukemia ◽  
Gene Single Nucleotide Polymorphism ◽  
Acute Myeloid
Sign in / Sign up

Export Citation Format

Share Document