Advances in Genomic Profiling and Risk Stratification in Acute Myeloid Leukemia

Richardson, Daniel R.; Foster, Matthew C.; Coombs, Catherine C.; Zeidner, Joshua F.

doi:10.1016/j.soncn.2019.150957

Cited by 7 publications

(4 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNMT3A, FLT3, IDH1, IDH2, and NPM1 are among the most commonly mutated loci [3,4]. Recent advances in genomics is improving patient stratification, allowing for better therapeutic regimens [5,6]. However, the prognosis remains bleak and a deeper understanding of the underlying mechanistic causes of AML remains absolutely necessary to accelerate the development of effective therapies.…”

Section: Introductionmentioning

confidence: 99%

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

et al. 2021

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) underlies the uncontrolled accumulation of immature myeloid blasts. Several cytogenetic abnormalities have been associated with AML. Among these is the NUP98-HOXA9 (NA9) translocation that fuses the Phe-Gly repeats of nucleoporin NUP98 to the homeodomain of the transcription factor HOXA9. The mechanisms enabling NA9-induced leukemia are poorly understood. Here, we conducted a genetic screen in Drosophila for modifiers of NA9. The screen uncovered 29 complementation groups, including genes with mammalian homologs known to impinge on NA9 activity. Markedly, the modifiers encompassed a diversity of functional categories, suggesting that NA9 perturbs multiple intracellular events. Unexpectedly, we discovered that NA9 promotes cell fate transdetermination and that this phenomenon is greatly influenced by NA9 modifiers involved in epigenetic regulation. Together, our work reveals a network of genes functionally connected to NA9 that not only provides insights into its mechanism of action, but also represents potential therapeutic targets.

show abstract

Section: Introductionmentioning

confidence: 99%

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, a novel treatment, effective enough to eliminate cancer cells with minimal influence on normal bodily functions, is needed, especially for pediatric AML patients. Large‐scale sequencing and transcriptomics studies of AML patients have identified several novel targets for drug development 11‐13 . One of them, Polo‐like kinase 1 (Plk1), has been in the focus of AML drug design since its discovery 14 …”

Section: Introductionmentioning

confidence: 99%

“…Large-scale sequencing and transcriptomics studies of AML patients have identified several novel targets for drug development. [11][12][13] One of them, Polo-like kinase 1 (Plk1), has been in the focus of AML drug design since its discovery. 14 Plk1 is a serine-threonine kinase with essential roles in cell division.…”

mentioning

confidence: 99%

RNAi prodrugs decrease elevated mRNA levels of Polo‐like kinase 1 in ex vivo cultured primary cells from pediatric acute myeloid leukemia patients

et al. 2021

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a genetically heterogeneous disease that originates from mutations in the myeloid compartment of hematopoietic cells. Of all leukemia types, AML is the most refractory to treatment and the five-year survival ranges from 40% in adults to about 70% in children. 1 Induction treatment-resistant and relapsing cases have poor prognosis. 2,3 The high incidence of treatment-related deaths indicates that the use of chemotherapy has reached its limits and other treatment options should be developed to cure more patients. 4,5 Allogeneic stem cell transplantation is one of the approaches that is used in AML when other therapy options are exhausted. 6 Moreover, pediatric patients who recover

show abstract

“…Acute myeloid leukemia (AML), the most common acute leukemia in adults, is a heterogeneous group of leukemias characterized by aberrant clone transformation of hematopoietic precursors through the acquisition of chromosomal arrangements and abnormal gene expression patterns, exhibiting partial or complete arrest of maturation in the bone marrow, peripheral blood or other tissues ( 1 ). With application and refinement of the detection methodology such as chromosome banding, fluorescence in situ hybridization/chromosomal painting and the next generation sequencing, there have been incremental understanding of abnormal genetic and molecular alterations in the pathogenesis of AML ( 2 ).With these efforts, it is gradually accepted that AML is rather an umbrella diagnosis that comprises diverse subtypes with different prognostic and predictive markers, which are recommended for distinguished classification criteria and require selective and possible targeted therapies ( 3 , 4 ). However, approximately half of AML patients lack predicable or prognostic biomarker and widely variable transcriptome data and the overall prognosis remains dismal [5-year overall survival 28.7%] ( 5 ), highlighting the need for identifying novel genetic and molecular predictors.…”

Section: Introductionmentioning

confidence: 99%

Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis

2023

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is one of the most common malignant blood neoplasma in adults. The prominent disease heterogeneity makes it challenging to foresee patient survival. Autophagy, a highly conserved degradative process, played indispensable and context-dependent roles in AML. However, it remains elusive whether autophagy-associated stratification could accurately predict prognosis of AML patients. Here, we developed a prognostic model based on autophagy-associated genes, and constructed scoring systems that help to predicte the survival of AML patients in both TCGA data and independent AML cohorts. The Nomogram model also confirmed the autophagy-associated model by showing the high concordance between observed and predicted survivals. Additionally, pathway enrichment analysis and protein-protein interaction network unveiled functional signaling pathways that were associated with autophagy. Altogether, we constructed the autophagy-associated prognostic model that might be likely to predict outcome for AML patients, providing insights into the biological risk stratification strategies and potential therapeutic targets.

show abstract

Advances in Genomic Profiling and Risk Stratification in Acute Myeloid Leukemia

Cited by 7 publications

References 62 publications

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

A genetic screen in Drosophila uncovers the multifaceted properties of the NUP98-HOXA9 oncogene

RNAi prodrugs decrease elevated mRNA levels of Polo‐like kinase 1 in ex vivo cultured primary cells from pediatric acute myeloid leukemia patients

Identification of autophagy-associated genes and prognostic implications in adults with acute myeloid leukemia by integrated bioinformatics analysis

Contact Info

Product

Resources

About