ORCID Profile
0000-0001-9048-9580
Current Organisation
Peter MacCallum Cancer Centre
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2018
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.LEUKRES.2017.02.010
Abstract: miR-155 has emerged as one of the key microRNAs (miRNAs) involved in normal and malignant myelopoiesis, and high expression of this miRNA has been flagged as a strong independent prognostic marker in Acute Myeloid Leukemia (AML). While elevated expression of miR-155 has been associated with FLT3-ITD mutations, other mechanisms which may regulate expression of this miRNA in AML remain largely unknown. Here, we present new evidence that miR-155 may be a prime target of IL-3 signaling in primary AML cells. This finding, together with the increasingly apparent role for miR-155 in oncogenesis, and the upregulation of the IL-3 receptor alpha subunit in AML, lead us to propose this pathway may significantly contribute to the leukemic transformation.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 21-09-2017
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.CANCERGEN.2017.07.008
Abstract: We report a novel somatic mutation in the kinase domain of JAK2 (R938Q) in a high-risk pediatric case of B-cell acute lymphoblastic leukemia (ALL). The patient developed on-therapy relapse at 12 months, and interestingly, the JAK2 locus acquired loss of heterozygosity during treatment resulting in 100% mutation load. Furthermore, we show that primary ALL mononuclear cells harboring the JAK2 R938Q mutation display reduced sensitivity to the JAK1/2 ATP-competitive inhibitor ruxolitinib in vitro, compared to ALL cells that carry a more common JAK2 pseudokinase domain mutation. Our findings are in line with previous reports that demonstrate that mutations within the kinase domain of JAK2 are associated with resistance to type I JAK inhibitors. Importantly, given the recent inclusion of ruxolitinib in trial protocols for children with JAK pathway alterations, we predict that inter-patient genetic variability may result in suboptimal responses to JAK inhibitor therapy in a subset of cases. The need for alternate targeted and/or combination therapies for patients who display inherent or developed resistance to JAK inhibitor therapy will be warranted, and we propose that kinase-mutants less sensitive to type I JAK inhibitors may present a currently unexplored platform for investigation of improved therapies.
Publisher: Proceedings of the National Academy of Sciences
Date: 02-02-2021
Publisher: Springer Science and Business Media LLC
Date: 04-11-2020
Publisher: Oxford University Press (OUP)
Date: 05-03-2014
Abstract: Aberrant activation of β-catenin is a common event in AML and is an independent predictor of poor prognosis. Although increased β-catenin signaling in AML has been associated with oncogenic translocation products and activating mutations in the FLT3R, the mechanisms that activate β-catenin in AML more broadly are still unclear. Here, we describe a novel link between IL-3 signaling and the regulation of β-catenin in myeloid transformation and AML. In a murine model of HoxB8 and IL-3 cooperation, we show that β-catenin protein levels are modulated by IL-3 and that Cre-induced deletion of β-catenin abolishes IL-3-dependent growth and colony formation. In IL-3-dependent leukemic TF-1.8 cells, we observed increased β-catenin protein levels and nuclear localization in response to IL-3, and this correlated with transcriptional induction of β-catenin target genes. Furthermore, IL-3 promoted β-catenin accumulation in a subset of AML patient s les, and gene-expression profiling of these cells revealed induction of WNT/β-catenin and TCF4 gene signatures in an IL-3-dependent manner. This study is the first to link β-catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of β-catenin activity in some patients with AML.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2020
Publisher: Annual Reviews
Date: 24-01-2020
Publisher: Elsevier BV
Date: 2011
Publisher: Elsevier BV
Date: 11-2017
Publisher: Cold Spring Harbor Laboratory
Date: 05-04-2023
DOI: 10.1101/2023.04.05.535648
Abstract: T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive and heterogenous haematological malignancy affecting both children and adults. T-ALL subtype identification is an emerging area of active research, with several recent studies proposing potential subtypes based on transcriptomic and genomic analyses. Here we present TALLSorts, a machine-learning bioinformatic tool which classifies T-ALL s les by using bulk RNA sequencing (RNA-seq) data. Trained on four international cohorts totalling 264 s les, TALLSorts exhibits excellent accuracy when tested on holdout and independent test sets. TALLSorts is publicly available for use and will be constantly updated as the field of T-ALL classification further develops.
No related grants have been discovered for Teresa Sadras.