Dr Claire Lucas

Associate Professor

Chester Medical School
Dr Claire Lucas

Dr Claire Lucas  joined Chester Medical School as a Haematology Lecturer. Claire has over 15 years’ experience working as a NHS Scientist and Honorary lecturer.  Claire’s research area of expertise is biomarkers predictive of clinical outcome in leukaemia.

Prior to joining Chester Medical School, Claire worked in the NHS for 15 years  as a NHS Scientist at Royal Liverpool University Hospital. Claire worked in the department of Molecular Genetics, which is part of the Haematology-Oncology Diagnostics Service (HODS). She specialised in diagnosing patients with chronic myeloid leukaemia (CML). Claire has a diverse research portfolio which includes biomarkers predictive of clinical outcome and identifying novel therapeutic targets in CML and AML. To date, Claire’s most successful work has been on the biomarker CIP2A. Her work has shown that assessing CIP2A protein level at diagnosis of CML can predict patients who will subsequently progress to blast crisis, which is usually fatal. It is hoped that this CIP2A biomarker will be used in clinical practice in the future and lead to the personalisation of therapy.

Claire is the programme leader for MSc Haematology and teaches on both the undergraduate and postgraduate courses offered by Chester Medical School. She is module leader for

MD6031 Haematology and Transfusion Science.

MD6903 Blood Science (DL)

MD7005 Blood Science

MD7022 Therapeutic Advances in Treating Haematological Problems

In addition to being the MSc Haematology programme lead and module lead. I also teach across the Faculty of Medicine, Dentistry and Life Sciences. I frequently teach across the levels and programmes including BSc Biomedical Science, BMedSci Medical Science, BSc Microbiology, BSc Pharmacology, BSc Biochemistry, MSc Biomedical Science, MSc Infection and Immunity, MSc Medical Genetics, MSc Oncology and Physician Associate programmes.

I teach regularly on the following modules.

  • MD5016 Pathophysiology
  • MD5018 Diagnostics and Therapeutics
  • MD5027 Professional Skills for Life Science 2
  • MD6029 Dissertation
  • MD7006 Clinical Immunology
  • MD7024 Molecular Medicine
  • MD7058 Foundations of Clinical Medical Science
  • MD7100 Research dissertations

Claire also supervises and supports undergraduate and postgraduate students through their research dissertations and is a PhD supervisor and the Medicals Schools Postgraduate Research Tutor.

While working in the NHS Claire developed a keen interest in research and began to study for a part-time PhD in 2006 under the supervision of Prof Richard Clark. The title of her thesis  was “Biomarkers predictive of clinical outcome in chronic myeloid leukaemia (CML).” 

Claire's current research portfolio is a balance of translational and basic science research. Her area of expertise is biomarkers predictive of clinical outcome in both chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML). CML is a cancer of the haematopoietic stem cells. The aim of her research is to address three important questions:

1. Can we predict patients at diagnosis who will progress into blast crisis?

For some patients their disease will progress to an aggressive/fatal phase known as blast crisis (BC). Patients who develop blast crisis have a very poor clinical outcome, with a long term overall-survival of <20%. The mechanisms underlying the evolution of blast crisis are poorly understood and blast crisis remains a significant challenge for clinicians and scientists. I have identified a novel protein known as Cancerous Inhibitor of PP2A (CIP2A) as a biomarker which can identify at diagnosis those patients at risk of blast crisis. (Lucas et al. 2015; Lucas CM et al. 2011). I have shown that CIP2A confers the poorest clinical outcome by creating anti-apoptotic phenotype. (Lucas et al. 2016).

2. Can we predict those patients who can successfully stop treatment?

Some patients respond well to treatment but will remain on treatment indefinitely, with enduring side effects, impacting on their quality of life. My preliminary data indicates that changes in expression of an anti-apoptotic protein during treatment de-escalation may be a novel biomarker of molecular relapse. The aim here is to test this biomarker in the DESTINY clinical trial and it is hoped that this will identify patients who can successful stop treatment without relapsing. This will have both beneficial outcomes for the patient and may prove advantageous financially to Healthcare Trusts. 

3. Identify novel therapeutic targets to eliminate the residual leukaemic stem cells (LSC) and potentially cure the disease.

CML LSC are responsible for initiation and relapse of the disease. Treatment involves BCR-ABL tyrosine kinase inhibitors which do not kill LSC. CML will only be cured when LSC are eradicated. There is an urgent need to identify new LSC therapeutic targets. I am currently working on two potential novel targets.

Di Mambro A, Arroyo-Berdugo Y, Fioretti T, Randles M, Cozzuto L, Rajeeve V, Cevenini A, Austin MJ, Esposito G, Ponomarenko J, Lucas CM, Cutillas P, Gribben J, Williams O, Calle Y, Patel B, Esposito MT. SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML. Oncogene. 2023 Oct 27. doi: 10.1038/s41388-023-02840-1. Epub ahead of print. PMID: 37891368.

Saifullah HH, Lucas CM. Treatment-Free Remission in Chronic Myeloid Leukemia: Can We Identify Prognostic Factors? Cancers (Basel). 2021;13(16).

Clark RE, Austin GM, Holcroft AK, Bonnett L, Scott L, Loaiza S, Apperley J, Law C, Lucas CM. Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia. Cancers. 2021;13(9):2155.

Makela E, Pavic K, Varila TM, Salmenniemi U, Löyttyniemi E, Nagelli SG, Ammunét T, Kähäri VM, Clark, RE, Elo LL, Bachanaboyina VK, Lucas CM*, Itälä-Remes M, & Westermarck J. Discovery of a Novel CIP2A Variant (NOCIVA) with clinical relevance in predicting TKI resistance in myeloid leukemias. Clinical Cancer Research. 2021: clincanres.3679.2020. *Senior UK investigator

Perrotti D, Agarwal A, Lucas CM, et al. Comment on "PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL human leukemia". Sci Transl Med. 2019;11(501).

Austin JA, Jenkins RE, Austin GM, Glenn MA, Dunn K, Scott L, Lucas CM*, Clark RE*.  Cancerous inhibitor of protein phosphatase 2A (CIP2A) modifies energy metabolism via 5' AMP-activated protein kinase signalling in malignant cells. Biochem J. 2019;476(15):2255-2269.

Lucas CM, Scott LJ, Carmell N, et al. CIP2A- and SETBP1-mediated PP2A inhibition reveals AKT S473 phosphorylation to be a new biomarker in AML. Blood Adv. 2018;2(9):964-968.

Lucas CM, Milani M, Butterworth M, et al. High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia. Leukemia. 2016;30(6):1273-1281.

Lucas CM, Harris RJ, Holcroft AK, et al. Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients. Leukemia. 2015;29(7):1514-1523.

Lucas CM, Harris RJ, Giannoudis A, Clark RE. c-Myc inhibition decreases CIP2A and reduces BCR-ABL1 tyrosine kinase activity in chronic myeloid leukemia. Haematologica. 2015;100(5): e179-e182.

Giannoudis A, Davies A, Harris RJ, Lucas CM, Pirmohamed M, Clark RE. The clinical significance of ABCC3 as an imatinib transporter in chronic myeloid leukaemia. Leukemia. 2014;28(6):1360-1363.

Lucas CM, Harris RJ, Giannoudis A, McDonald E, Clark RE. Low leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemia. Haematologica. 2014;99(11):1710-1715.

Neelakantan P, Gerrard G, Lucas C, et al. Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies. Blood. 2013;121(14):2739-2742.

Francis S, Lucas C, Lane S, et al. A population study showing that the advent of second generation tyrosine kinase inhibitors has improved progression-free survival in chronic myeloid leukaemia. Leuk Res. 2013;37(7):752-758.

Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30(3):232-238.

Lucas CM, Harris RJ, Giannoudis A, Copland M, Slupsky JR, Clark RE. Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood. 2011;117(24):6660-6668.

Lucas CM, Fagan JL, Carter A, et al. Rapid diagnosis of chronic myeloid leukemia by flow cytometric detection of BCR-ABL1 protein. Haematologica. 2011;96(7):1077-1078.

Lucas CM, Harris RJ, Giannoudis A, Davies A, Clark RE. SET Binding Protein 1 expression does not predict clinical outcome in chronic myeloid leukaemia. eBlood. 2010.

Lucas CM, Harris RJ, Giannoudis A, Knight K, Watmough SJ, Clark RE. BCR-ABL1 tyrosine kinase activity at diagnosis, as determined via the pCrkL/CrkL ratio, is predictive of clinical outcome in chronic myeloid leukaemia. British Journal of Haematology. 2010;149(3):458-460

Davies A, Jordanides NE, Giannoudis A, Lucas CM, et al. Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009;23(11):1999-2006.

Lucas CM, Harris RJ, Giannoudis A, et al. Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript. Haematologica. 2009;94(10):1362-1367.

Giannoudis A, Davies A, Lucas CM, Harris RJ, Pirmohamed M, Clark RE. Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood. 2008;112(8):3348-3354.

Lucas CM, Wang L, Austin GM, et al. A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Leukemia. 2008;22(10):1963-1966.

Wang L, Knight K, Lucas C, Clark RE. The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia. Haematologica. 2006;91(2):235-239.

 

Conference Presentations (2010 onwards)

John Goldman Conference on Chronic Myeloid Leukaemia: Biology and Therapy 2023 – Mandelieu-La Napoule, France.

British society of Haematology meeting 2020 –Birmingham, UK - Oral presentation (Top scoring abstract)

European school of Haematology CML meeting 2019 – Bordeaux, France. – Oral presentation and a poster

British society of Haematology meeting 2019 –Glasgow, UK - Oral presentation (Top scoring abstract) and a poster

European school of Haematology CML meeting 2018 – Miami, USA. – Oral presentation and a poster

British Lymphoma Society meeting 2018 - Liverpool, UK – Invited speaker

British society of Haematology meeting 2018 –Liverpool, UK - Poster

European school of Haematology CML meeting 2017 – Estoril, Portugal – Invited speaker

European school of Haematology CML meeting 2015 – Estoril, Portugal  – Invited speaker

European Haematology Association annual conference 2014  Vienna, Austria. – Three oral presentations.

European school of Haematology CML meeting 2014 – Philadelphia, PA, USA. – Invited speaker

European school of Haematology CML meeting 2013 – Estoril, Portugal – Invited speaker

European Haematology Association annual conference 2013 Stockholm, Sweden. Poster

European Haematology Association annual conference 2012 – Amsterdam, Netherlands - Poster

European Haematology Association annual conference 2011 – London UK. – Two oral presentations.

European school of Haematology CML meeting 2010 – Washington, USA. – Invited speaker.

  • 2021. Fellow of the Higher Education Academy (FHEA)
  • 2021. Postgraduate certificate in Learning and Teaching in Higher Education, University of Chester
  • 2020.  Associate Fellow of the Higher Education Academy (AFHEA)
  • 2011. PhD, Faculty of Medicine, University of Liverpool.
  • 2003. BSc (Hons) Physiology, Department of Physiology, University of Liverpool.