Tessa L. Holyoake
University of Glasgow
ImmunologyImatinibStem cellCancer researchMedicine
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Publications 313
#1Gillian A. Horne (Glas.: University of Glasgow)H-Index: 6
#2Jon Stobo (Glas.: University of Glasgow)H-Index: 5
Last. Mhairi Copland (Glas.: University of Glasgow)H-Index: 28
view all 23 authors...
In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-tw...
4 CitationsSource
#1Ross Kinstrie (Glas.: University of Glasgow)H-Index: 10
#2Gillian A. Horne (Glas.: University of Glasgow)H-Index: 6
Last. Mhairi Copland (Glas.: University of Glasgow)H-Index: 28
view all 16 authors...
The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed “minimal residual disease”. The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, BCR-ABL-independent mechanisms exist which sustain the survival of leukemic stem cells (LSCs). Although other markers of a primitive CML LSC population...
1 CitationsSource
Last. David VetrieH-Index: 32
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#1Pablo Baquero (Glas.: University of Glasgow)H-Index: 6
#2Amy Dawson (Glas.: University of Glasgow)H-Index: 2
Last. G. Vignir Helgason (Glas.: University of Glasgow)H-Index: 12
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In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cel...
14 CitationsSource
#1Francesca Pellicano (Glas.: University of Glasgow)H-Index: 15
#2Laura Park (Glas.: University of Glasgow)H-Index: 4
Last. Tessa L. Holyoake (Glas.: University of Glasgow)H-Index: 53
view all 17 authors...
Chronic myeloid leukemia (CML) stem/progenitor cells (SPC) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPC maintain quiescence will help to clarify how they persist during long-term targeted treatment. We have identified a novel BCR-ABL1 protein kinase dependent pathway mediated by the up-regulation of hsa-mir183, the down-regulation of its direct target EGR1 and, as a consequence, up-r...
4 CitationsSource
#1Bin Zhang (City of Hope National Medical Center)H-Index: 16
#2Le Xuan Truong Nguyen (City of Hope National Medical Center)H-Index: 2
Last. Guido Marcucci (City of Hope National Medical Center)H-Index: 19
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In chronic myelogenous leukemia, leukemia stem cell function requires a microRNA that is provided by bone marrow endothelial cells.
14 CitationsSource
#1Hein Than (UofU: University of Utah)H-Index: 1
#2Anthony D. Pomicter (UofU: University of Utah)H-Index: 8
Last. Michael W. Deininger (UofU: University of Utah)H-Index: 76
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Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy driven by BCR-ABL1 tyrosine kinase and effectively managed with tyrosine kinase inhibitors (TKIs) such as imatinib. Reactivation of BCR-ABL1 through mutations in the kinase is a common mechanism of resistance, but fails to explain clinical resistance in a significant proportion of cases, a situation referred to as BCR-ABL1-independent resistance. Additionally, most patients require continuous TKI therapy to avoid recurrence o...
1 Citations
#1Lorna Jackson (Glas.: University of Glasgow)H-Index: 2
#2Eduardo Gómez-Castañeda (Glas.: University of Glasgow)H-Index: 1
Last. Xu Huang (Glas.: University of Glasgow)H-Index: 38
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Oncogene addiction is the dependence seen in some types of cancer cells on the presence or activity of an oncogene. Chronic myeloid leukaemia (CML) is driven by the BCR-ABL1 oncogene. CML has become a paradigm for targeted therapies, as the disease is effectively managed in most patients by BCR-ABL1 inhibitors. Although the symptom-causing leukaemic progenitor cells depend on the kinase activity of BCR-ABL1 for survival, the more primitive leukaemia stem cells (LSCs) responsible for disease main...
#1Kourosh Hayatigolkhatmi (Glas.: University of Glasgow)H-Index: 1
#2G. Padroni (University of Strathclyde)H-Index: 3
Last. Heather G. Jørgensen (Glas.: University of Glasgow)H-Index: 26
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3 CitationsSource
#1Elodie M. KuntzH-Index: 3
#2Pablo BaqueroH-Index: 6
Last. Eyal GottliebH-Index: 57
view all 8 authors...
Treatment with tyrosine kinase inhibitors results in a survival benefit in patients with chronic myeloid leukemia (CML). However, relapse due to persistent leukemic stem cells (LSCs) requires additional selective targets for efficient eradication of the disease. Metabolomic analyses on patient-derived CML LSCs reveal that these have an increased dependency on oxidative metabolism that renders them sensitive to treatment with tigecycline, an FDA-approved inhibitor of mitochondrial translation. Th...
79 CitationsSource