Outputs (18)

Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML (2023)
Journal Article
James, J. R., Curd, J., Ashworth, J. C., Abuhantash, M., Grundy, M., Seedhouse, C. H., Arkill, K. P., Wright, A. J., Merry, C. L. R., & Thompson, A. (2023). Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML. International Journal of Molecular Sciences, 24(4), Article 4235. https://doi.org/10.3390/ijms24044235

In vivo models of acute myeloid leukemia (AML) are low throughput, and standard liquid culture models fail to recapitulate the mechanical and biochemical properties of the extracellular matrix-rich protective bone marrow niche that contributes to dru... Read More about Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.

Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux (2022)
Journal Article
Nicholson, R., Menezes, A., Azevedo, A., Leckenby, A., Davies, S., Seedhouse, C., Gilkes, A., Knapper, S., Tonks, A., & Darley, R. L. (2022). Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux. Frontiers in Oncology, 12, Article 840046. https://doi.org/10.3389/fonc.2022.840046

The protein kinase C (PKC) family of serine/threonine kinases are pleiotropic signaling regulators and are implicated in hematopoietic signaling and development. Only one isoform however, PKCϵ, has oncogenic properties in solid cancers where it is as... Read More about Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux.

Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia (2020)
Journal Article
Bailey, G. D., Doolan, L., Baskar, A., Smith, L. C., & Seedhouse, C. H. (2020). Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia. Scientific Reports, 10, Article 17695. https://doi.org/10.1038/s41598-020-73782-x

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 (NPM1... Read More about Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia.

Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia (2012)
Journal Article
Jawad, M., Yu, N., Seedhouse, C., Tandon, K., Russell, N. H., & Pallis, M. (2012). Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia. BMC Cancer, https://doi.org/10.1186/1471-2407-12-431

Background
The CD34+CD38- subset of AML cells is enriched for resistance to current chemotherapeutic agents and considered to contribute to disease progression and relapse in Acute Myeloid Leukaemia (AML) patients following initial treatment.

Met... Read More about Targeting of CD34+CD38- cells using Gemtuzumab ozogamicin (Mylotarg) in combination with tipifarnib (Zarnestra) in acute Myeloid Leukaemia.

The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells (2012)
Journal Article
Pallis, M., Abdul-Aziz, A., Burrows, F., Seedhouse, C., Grundy, M., & Russell, N. (2012). The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells. British Journal of Haematology, 159(2), 191-203. https://doi.org/10.1111/bjh.12018

The novel multi-kinase inhibitor TG02 has selectivity against cell cycle and transcriptional cyclin dependent kinases (CDKs) as well as fms-like tyrosine kinase receptor-3 (FLT3). Inhibition of transcriptional CDKs preferentially depletes short-lived... Read More about The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells.

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA (2011)
Journal Article
Grundy, M., Seedhouse, C., Russell, N. H., & Pallis, M. (2011). P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA. BMC Cancer, 11, Article 254. https://doi.org/10.1186/1471-2407-11-254

Background
Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of... Read More about P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA.

The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells (2010)
Journal Article
Grundy, M., Seedhouse, C., Shang, S., Richardson, J., Russell, N., & Pallis, M. (2010). The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells. Molecular Cancer Therapeutics, 9(3), https://doi.org/10.1158/1535-7163.MCT-09-1144

Aurora kinases play an essential role in orchestrating chromosome alignment, segregation, and cytokinesis during mitotic progression and both aurora-A and B are frequently overexpressed in a variety of human malignancies. In this study, we report the... Read More about The FLT3 internal tandem duplication mutation is a secondary target of the aurora B kinase inhibitor AZD1152-HQPA in acute myelogenous leukemia cells.

Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine (2009)
Journal Article
Seedhouse, C., Grundy, M., Shang, S., Ronan, J., Pimblett, H., Russell, N., & Pallis, M. (2009). Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine. Clinical Cancer Research, 15(23), 7291-7298. https://doi.org/10.1158/1078-0432.CCR-09-1222

Purpose: Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show def... Read More about Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine.

Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia (2009)
Journal Article
Jawad, M., Seedhouse, C., Mony, U., Grundy, M., Russell, N. H., & Pallis, M. (2010). Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia. Leukemia, 24, 74-80. https://doi.org/10.1038/leu.2009.199

Relapse in acute myeloid leukaemia (AML) is considered to result from the persistence of drug-resistant leukaemic stem and progenitor cells (LSPC) within a bone marrow ‘niche’ microenvironment. Identifying novel agents that have the potential to targ... Read More about Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia.

Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment (2008)
Journal Article
(2008). Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment. Leukemia, 22, 1395-1401. https://doi.org/10.1038/leu.2008.125

Relapse in acute myeloid leukaemia (AML) is mediated by survival of leukaemic stem cells following remission-induction chemotherapy. It would therefore be useful to identify therapeutic agents that target leukaemic stem cells. We devised a flow cytom... Read More about Resistance to FLT3 inhibition in an in vitro model of primary AML cells with a stem cell phenotype in a defined microenvironment.