ORCID Profile
0000-0002-9619-0624
Current Organisation
University of South Australia
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Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709849.V1
Abstract: Summary of the key interactions in the IL-3R ternary complex in the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854334
Abstract: Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854331
Abstract: Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in in vivo engraftments.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709855.V1
Abstract: Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in in vivo engraftments.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854325.V1
Abstract: Summary of the key interactions in the IL-3R ternary complex in the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709870.V1
Abstract: Key interactions between distinct residues in the IL-3R ternary complex crystal structure.
Publisher: Oxford University Press (OUP)
Date: 30-06-2011
DOI: 10.1093/HMG/DDR292
Publisher: Oxford University Press (OUP)
Date: 25-04-2011
DOI: 10.1093/HMG/DDR177
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709873
Abstract: IL3Rα/βc transcript and protein expression ratio in AML patient s les.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709870
Abstract: Key interactions between distinct residues in the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709858.V1
Abstract: Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709861.V1
Abstract: Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854334.V1
Abstract: Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.
Publisher: American Association for Cancer Research (AACR)
Date: 20-08-0006
DOI: 10.1158/2159-8290.23854328.V1
Abstract: Data collection and refinement statistics for the IL-3R ternary complex crystal structure.
Publisher: Elsevier BV
Date: 2011
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2019
DOI: 10.1158/2159-8290.23854361
Abstract: IL3Rα/βc transcript and protein expression ratio in AML patient s les.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709867.V1
Abstract: IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709864
Abstract: The IL-3R dodecamer activates STAT1 to induce cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709861
Abstract: Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.
Publisher: Cognizant, LLC
Date: 20-12-2013
Publisher: Humana Press
Date: 2013
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709864.V1
Abstract: The IL-3R dodecamer activates STAT1 to induce cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854361.V1
Abstract: IL3Rα/βc transcript and protein expression ratio in AML patient s les.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854340.V1
Abstract: Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.
Publisher: Springer Science and Business Media LLC
Date: 06-1201
Publisher: American Society of Hematology
Date: 23-01-2020
DOI: 10.1182/BLOODADVANCES.2019000586
Abstract: Cyclin-dependent kinase 9 and bromodomain and extraterminal inhibitors are synergistic in MLL-rearranged leukemia. Multiple AML driver genes are downregulated by the combined therapy suggesting broad applicability for this subtype.
Publisher: American Society of Hematology
Date: 02-12-2021
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854328
Abstract: Data collection and refinement statistics for the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709867
Abstract: IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854325
Abstract: Summary of the key interactions in the IL-3R ternary complex in the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.C.6749895.V2
Abstract: Abstract Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the in idual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance. Significance: Stemness is a hallmark of many cancers and is largely responsible for disease emergence, progression, and relapse. Our finding that clinically significant stemness programs in AML are directly regulated by different stoichiometries of cytokine receptors represents a hitherto unexplained mechanism underlying cell-fate decisions in cancer stem cell hierarchies. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-13-8-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 1749 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.C.6749895.V1
Abstract: Abstract Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the in idual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance. Significance: Stemness is a hallmark of many cancers and is largely responsible for disease emergence, progression, and relapse. Our finding that clinically significant stemness programs in AML are directly regulated by different stoichiometries of cytokine receptors represents a hitherto unexplained mechanism underlying cell-fate decisions in cancer stem cell hierarchies. /
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854355
Abstract: Key interactions between distinct residues in the IL-3R ternary complex crystal structure.
Publisher: Royal Society of Chemistry (RSC)
Date: 1999
DOI: 10.1039/A809571J
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854352
Abstract: IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.
Publisher: Springer Science and Business Media LLC
Date: 15-07-2022
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854346.V1
Abstract: The IL-3R dodecamer activates STAT1 to induce cell differentiation.
Publisher: Oxford University Press (OUP)
Date: 21-03-2013
DOI: 10.1093/HMG/DDT130
Publisher: Frontiers Media SA
Date: 2013
Publisher: Massachusetts Medical Society
Date: 27-07-2000
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709852
Abstract: Data collection and refinement statistics for the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.C.6749895
Abstract: Abstract Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the in idual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance. Significance: Stemness is a hallmark of many cancers and is largely responsible for disease emergence, progression, and relapse. Our finding that clinically significant stemness programs in AML are directly regulated by different stoichiometries of cytokine receptors represents a hitherto unexplained mechanism underlying cell-fate decisions in cancer stem cell hierarchies. i a href="ancerdiscovery/article/doi/10.1158/2159-8290.CD-13-8-ITI" target="_blank" This article is highlighted in the In This Issue feature, p. 1749 /a /i /
Publisher: American Association for Cancer Research (AACR)
Date: 16-05-2023
DOI: 10.1158/2159-8290.CD-22-1396
Abstract: Stemness is a hallmark of many cancers and is largely responsible for disease emergence, progression, and relapse. Our finding that clinically significant stemness programs in AML are directly regulated by different stoichiometries of cytokine receptors represents a hitherto unexplained mechanism underlying cell-fate decisions in cancer stem cell hierarchies. This article is highlighted in the In This Issue feature, p. 1749
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854355.V1
Abstract: Key interactions between distinct residues in the IL-3R ternary complex crystal structure.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709858
Abstract: Increasing IL3Rα/βc ratios lead to hexameric receptor assembly and augmented quiescence.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2022
DOI: 10.1038/S41467-022-30223-9
Abstract: The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) and show that rare variants affecting the nuclear- and mitochondrially-encoded complex I genes show near-mutual exclusivity with somatic driver mutations affecting isocitrate dehydrogenase 1 ( IDH1 ), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells with rare complex I variants or mutations in IDH1 or IDH2 all display attenuated mitochondrial respiration, heightened sensitivity to complex I inhibitors including the clinical-grade inhibitor, IACS-010759, is observed only for IDH1 -mutant AML. Furthermore, IDH1 mutant blasts that are resistant to the IDH1-mutant inhibitor, ivosidenib, retain sensitivity to complex I inhibition. We propose that the IDH1 mutation limits the flexibility for citrate utilization in the presence of impaired complex I activity to a degree that is not apparent in IDH2 mutant cells, exposing a mutation-specific metabolic vulnerability. This reduced metabolic plasticity explains the epistatic relationship between the germline complex I variants and oncogenic IDH1 mutation underscoring the utility of genomic data in revealing metabolic vulnerabilities with implications for therapy.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709855
Abstract: Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in in vivo engraftments.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854346
Abstract: The IL-3R dodecamer activates STAT1 to induce cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854340
Abstract: Enrichment of the IL-3R hexamer versus dodecamer gene signature in primitive normal and leukemic stem cells.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709873.V1
Abstract: IL3Rα/βc transcript and protein expression ratio in AML patient s les.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709852.V1
Abstract: Data collection and refinement statistics for the IL-3R ternary complex crystal structure.
Publisher: American Society of Hematology
Date: 09-02-2017
DOI: 10.1182/BLOOD-2016-06-720433
Abstract: Inhibition of SPHK1 in human AML cells induces MCL1 degradation and caspase-dependent cell death. SPHK1 inhibitors reduce leukemic burden and prolong survival in orthotopic patient-derived xenografts of AML.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854331.V1
Abstract: Increasing IL3Rα/βc ratios and enforced hexamer signaling lead to reduced differentiation in in vivo engraftments.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.PATHOL.2022.05.015
Abstract: The identification of a somatic mutation associated with myeloid malignancy is of diagnostic importance in myeloproliferative neoplasms (MPNs). In iduals with no mutation detected in common screening tests for variants in JAK2, CALR, and MPL are described as 'triple-negative' and pose a diagnostic challenge if there is no other evidence of a clonal disorder. To identify potential drivers that might explain the clinical phenotype, we used an extended sequencing panel to characterise a cohort of 44 previously diagnosed triple-negative MPN patients for canonical mutations in JAK2, MPL and CALR at low variant allele frequency (found in 4/44 patients), less common variants in the JAK-STAT signalling pathway (12 patients), or other variants in recurrently mutated genes from myeloid malignancies (18 patients), including hotspot variants of potential clinical relevance in eight patients. In one patient with thrombocytosis we identified biallelic germline MPL variants. Neither MPL variant was activating in cell proliferation assays, and one of the variants was not expressed on the cell surface, yet co-expression of both variants led to thrombopoietin hypersensitivity. Our results highlight the clinical value of extended sequencing including germline variant analysis and illustrate the need for detailed functional assays to determine whether rare variants in JAK2 or MPL are pathogenic.
Publisher: American Association for Cancer Research (AACR)
Date: 04-08-2023
DOI: 10.1158/2159-8290.23854352.V1
Abstract: IL3Rα P248 at the IL-3R assembly interface is critical for cell differentiation.
Publisher: American Association for Cancer Research (AACR)
Date: 19-07-2023
DOI: 10.1158/2159-8290.23709849
Abstract: Summary of the key interactions in the IL-3R ternary complex in the IL-3R ternary complex crystal structure.
Publisher: Public Library of Science (PLoS)
Date: 08-06-2012
Publisher: Elsevier BV
Date: 07-2023
No related grants have been discovered for Saumya Samaraweera.