Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome
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PROVIDER: PRJNA1270095 | ENA |
REPOSITORIES: ENA
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Project description:Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome
| PRJNA1270094 | ENA
Project description:Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically improved in the past 40 years, currently reaching 70% to 80% in developed countries. This was accomplished by the intensification of conventional chemotherapy, improvement in risk stratification using leukemia-specific cytogenetics/molecular genetics and measurable residual disease, appropriate use of allogeneic hematopoietic stem cell transplantation, and improvement in supportive care. However, the principle therapeutic approach for pediatric AML has not changed substantially for decades and improvement in event-free survival is rather modest. Further refinements in risk stratification and the introduction of emerging novel therapies to contemporary therapy, through international collaboration, would be key solutions for further improvements in outcomes.
| S-EPMC10452723 | biostudies-literature
Project description:Schizophrenia (SZ) is a devastating psychiatric illness affecting 1% of the world population. In addition to genetic predisposition, environmental factors contribute to the risk for developing SZ. Such genome environment interactions frequently activate epigenetic and epitranscriptomic mechansims. There are emerging evidence that genetic and environmental risk factors merge at the level of microRNA expression, which are discussed as biomarker and therapeutic target in various disorders including neuropsychiatric diseases. In this study we analyzed the blood microRNAome of healthy individuals and SZ patients via small RNA sequencing. By combining these data with a corresponding analysis of post-mortem human brain tissue, we identify one candidate microRNA that is down-regulated in patients. Moreover, its expression is significantly correlated to disease phenotypes. Manipulation of this microRNAs in mouse prefrontal cortex causes schizophrenia-like phenotypes. Functional analysis revealed the cellular processes affected by this microRNA and allowed us to develop an arsenal of RNA-based therapeutic approaches that are able to ameliorate molecular disease phenotypes in mouse and human-based cellular systems as well as the behavioral phenotypes. In conclusion, we identify a novel microRNA as target for stratified RNA-therapeutics in schizophrenia.
2024-03-26 | GSE224142 | GEO
Project description:INCLUDE: Mechanisms, Genomic Risk Stratification and Precision Intervention for Acute Myeloid Leukemia in Children with Down syndrome (ML-DS)
| PRJNA854740 | ENA
Project description:Down syndrome SNP genotyping data
| EGAD00010000464 | EGA
Project description:Down syndrome CNV genotyping data
| EGAD00010000466 | EGA
Project description:Although adults with Down syndrome (DS) show a decreased incidence of cancer compared to individuals without DS, children with DS are at an increased risk of leukemia. Nearly half of these childhood leukemias are classified as acute megakaryoblastic leukemia (AMKL), a relatively rare subtype of acute myeloid leukemia (AML). Here, we summarize the clinical features of myeloid leukemia in DS, review recent research on the mechanisms of leukemogenesis, including the roles of GATA1 mutations and trisomy 21, and discuss treatment strategies. Given that trisomy 21 is a relatively common event in hematologic malignancies, greater knowledge of how the genes on chromosome 21 contribute to DS-AMKL will increase our understanding of a broader class of patients with leukemia.
| S-EPMC3243928 | biostudies-literature
Project description:Increased levels of low-density lipoproteins are the main risk factor in the initiation and progression of atherosclerosis. Although statin treatment can effectively lower these levels, there is still a residual risk of cardiovascular events. A more recent therapy, with encouraging results, to regulate the low-density lipoproteins levels, has been represented by the proprotein convertase subtilisin/kexin type 9 inhibition, a protein with critical role in lipid metabolism.Alarmins are endogenous danger signals that are released or secreted from damaged or dead/dying cells as a result of various insults. These stress-sensing molecules have been correlated with various inflammatory states or diseases. We hypothesize that a specific panel of alarmins could indicate the persistence of silent atherosclerosis residual risk.
2022-10-03 | PXD035692 | Pride
Project description:This study aimed to identify whether c-Myc could facilitate prediction of "7+3" induction failure in de novo acute myeloid leukaemia (AML) with high-risk cytogenetics. Seventy-five untreated de novo AML patients who completed the "7+3" induction therapy were enrolled (24 patients from a prospective cohort; 51 patients from a retrospective cohort) and stratified into complete remission (CR) and non-CR groups. Myc-associated molecular signature between the CR and non-CR groups in the prospective cohort was compared after gene set enrichment analysis. c-Myc protein expression was assessed via immunohistochemical staining. A high c-Myc-immunopositivity was defined when ≥ 40% of bone marrow myeloblasts were c-Myc (+). Our results revealed that AML patients who did not achieve CR by the "7+3" induction therapy had a higher Myc gene expression than those that achieved CR (p=0.047). Myc gene expression was positively correlated with c-Myc protein expression (p=0.014). Although the non-CR group did not have more c-Myc protein expression compared to that in the CR group (p=0.151), combination of high c-Myc-immunopositivity and high-risk cytogenetics increased the probability of "7+3" induction failure compared to that in high-risk cytogenetics alone. Induction strategies other than “7+3” might be a solution for de novo patients with high c-Myc-immunopositivity and high-risk cytogenetics.
2021-04-01 | GSE164894 | GEO