Northern Institute for Cancer Research

Staff Profile

Professor Christine Harrison

Professor of Childhood Cancer Cytogenetics

Background

Christine J Harrison PhD FRCPath FMedSci

Professor of Childhood Cancer Cytogenetics

Leukaemia Research Cytogenetics Group

Wolfson Childhood Cancer Research Centre

Northern Institute for Cancer Research,

Level 6, Herschel Building

Newcastle University,

Newcastle upon Tyne

Phone: 0191 208 2237

email: christine.harrison@newcastle.ac.uk

Professor of Childhood Cancer Cytogenetics, Newcastle University 

Director, Centre for Haematological Oncology, Newcastle University

Director, Leukaemia Research Fund Cytogenetics Group

Fellow, Academy of Medical Sciences

Fellow, Royal College of Pathologists


Newcastle University, Vice Chancellor Academic Distinction Award 2017


Review panel, European Research Council

 

Review Panel, GILEAD

 

Review Panel, INcA

 

Review panel, Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek - Vlaanderen, FWO).

 

Research

The remit of my research is to improve outcome for patients with acute leukaemia through genetics in UK treatment trials, by characterisation of existing and discovery of novel genetic changes. I have over 30 years’ experience in planning and leading research activities of national/international repute in the area of cytogenetics/genetics of haematological malignancies. I was responsible for the initiation of a database for the cytogenetics of acute leukaemia in 1988, when the importance of chromosomal abnormalities in risk stratification for treatment was becoming evident. This has now developed into a large-scale collection of cytogenetic and genetic data, containing information on more than 28,000 UK patients, which is renowned to be one of the best leukaemia genetics research resources in the world. Some of the most recent analyses from these data have identified new cytogenetic-based risk categories in childhood and adult acute leukaemia, which have resulted in changes in clinical practice.

I have a passion for the development of new technologies. In the 1980’s, I pioneered studies on the scanning electron microscopy of metaphase chromosomes to provide increased resolution for detailed analysis at the structural level. The demand for images from these investigations continues to this day.

From studies on deletions of the long arm of chromosome 6 (6q) in acute leukaemia, I was one of the early pioneers of chromosome mapping using fluorescence in situ hybridisation (FISH)

I was responsible for the development of FISH for the detection of chromosomal abnormalities of prognostic significance in UK acute leukaemia clinical treatment trials. FISH is now used routinely in UK and has been adopted into trial protocols in Europe and internationally. This approach led to the discovery of novel chromosomal abnormalities for which modified treatment has significantly improved survival.

Within my group we provided early development of procedures for array-based comparative genomic hybridisation (aCGH) in acute leukaemia, which now is widely used for the detection of chromosomal imbalances, not only in leukaemia but a wide range of other cancers. Using this in association with other procedures, we have identified novel chromosomal abnormalities with potential as molecular targets for therapy. My current interests involve the application of next-generation sequencing to search for novel significant mutations in acute leukaemia. Understanding of the role of genetics in the improved survival of leukaemia patients is my ultimate aim.

Selected publications

  • O’Connor, D., Enshaei, A., Bartram, J., Hancock, J., Harrison, C.J., Hough, R.,  Samarasinghe, S., Schwab, C., Vora, A., Wade, R., Moppet, J., Moorman, A.V., Goulden, N. (2018)  Genotype-specific MRD interpretation improves stratification in paediatric acute lymphoblastic leukaemia. J Clin Oncol 36(1): 34-43
  • Schwab, C., Nebral, K., Chilton, L., Leschi, C., Waanders, E., Boer, J.M., Zaliova, M., Sutton, R., Öfverholm, I.I., Ohki, K., Yamashita, Y., Groeneveld-Krentz, S., Fro?ková, E., Bakkus, M., Tchinda, J., da Conceição Barbosa, T., Fazio, G., Mlynarski, W., Pastorczak, A., Cazzaniga, G., Pombo-de-Oliveira, M.S., Trka, J., Kirschner-Schwabe, R., Imamura, T., Barbany, G., Stanulla, M., Attarbaschi, A., Panzer-Grümayer, R., Kuiper, R.P., den Boer, M. L. Cavé, H., Moorman, A. V., Harrison, C.J. #, Strehl, S.# (#Joint senior authors) (2017) Intragenic amplification of PAX5: A novel subgroup in B-cell precursor acute lymphoblastic leukemia? Blood Advances
  • Russell, L.J., Jones, L., Enshaei, A., Tonin, S,, Ryan, S.L., Eswaran, J., Nakjang, S., Papaemmanuil, E., Tubio, J.M., Fielding, A.K., Vora, A., Campbell, P.J., Moorman, A.V., Harrison, C.J. (2017) Characterisation of the Genomic Landscape of CRLF2-rearranged Acute Lymphoblastic Leukemia. Genes, Chromosomes, Cancer 56(5): 363-72
  • Chilton, L.C., Harrison, C.J., Ashworth, I., Murdy, D., Burnett, A.K., Grimwade, D., Moorman, A.V., Hills, R (2017) Clinical relevance of failed and missing cytogenetic analysis in acute myeloid leukaemia (AML). Leukemia 31(5):1234-1237
  • O’Connor, D., Moorman, A.V., Wade, R., Hancock, J., Tan, R.M.R., Bartram, J., Moppett, J., Schwab, C.,  Patrick, K., Harrison, C.J., Hough, R., Goulden, N., Vora, A., Samarasinghe, S. (2016) Use of minimal residual disease assessment to redefine induction failure in pediatric acute lymphoblastic leukemia. J. Clin Oncol. 35(6): 660-7
  • Chilton, L., Hills, R.K., Burnett, A.K., Harrison, C.J. (2016) The prognostic significance of trisomy 4 in acute myeloid leukaemia (AML) is dependent on age and additional abnormalities. Leukemia 30(11): 2264-7
  • Ryan, S.L., Matheson, E., Grossmann, V., Sinclair, P., Bashton, M., Schwab, C., Towers, W., Partington, M., Elliott, A., Minto, L., Richardson, S., Rahman, T., Keavney, B., Skinner, R., Bown, N., Haferlach, T., Vandenberghe, P., Haferlach, C., Santibanez-Koref, M., Moorman, A.V., Kohlmann, A., Irving, J.A.E., Harrison, C.J. (2016) The role of the RAS pathway in iAMP21-ALL Leukemia (in press)
  • Moorman, A.V., Enshaei, A., Schwab, C., Chilton, L., Elliott, A., Richardson, S., Hancock, J., et al, Goulden, N., Vora, A. and Harrison, C.J.* (2014) A novel integrated cytogenetic and genomic classification refines risk stratification in paediatric acute lymphoblastic leukaemia (ALL). Blood 124 (9): 1434-44
  • Li, Y., Schwab, C., Ryan, S., Papaemmanuil, E., Heerema, N.A., Young, B.D., Stephens, P.J., et al, Stratton, M.R., Campbell, P.J.*?,Harrison, C.J.* ? (2014) Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia. Nature 508 (7494): 98-102 
  • Russell, L.J., Enshaei, A., Bentley, H., Fielding, A.K., et al, Goulden, N., Vora, A., Moorman, A.V., Harrison, C.J.* ? (2014) IGH@translocations are prevalent in teenagers and young adults with ALL and are associated with a poor outcome. J Clin Oncol 32 (14): 1453-62
  • Harrison, C.J. ?, Moorman, A.V., Schwab, C., Carroll, A.J., Raetz, E.A., Devidas, M., et al, Hunger, S.P., Heerema, N.A., Haas, O.A. (2014) An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome. Leukemia 28 (5): 1015-21
  • Moorman, AV., Robinson, H. Schwab, C., Richards, SM., Hancock, J., Mitchell, CD., Goulden, N., Vora, A., Harrison, C.J.* (2013) Risk-directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukemia and intrachromosomal amplification of chromosome 21: a comparison of the MRC ALL97/99 and UKALL2003 Trials. J Clin Oncol 31 (27): 3389-96. 
  • Moorman, A.V., Schwab, C., Ensor, H.M., Russell, L.J., et al, Patel, B., Rowe, J.M., Tallman, M., Goldstone, A.H., Fielding, A.K.,Harrison, C.J.* (2012) IGH@ translocations, CRLF2 deregulation and micro-deletions in adolescents and adults with acute lymphoblastic leukemia (ALL). J. Clin Oncol 30 (25); 3100-8 
  • Rand, V., Russell, L.J., Schwab, C., et al, Ryan, S., Robinson, H., et al, Sinclair, P., Moorman, A.V., Strefford, J.C.*, Harrison, C.J.* ?(2011) Genomic characterization implicates iAMP21 as a likely primary genetic event in childhood B-cell precursor acute lymphoblastic leukemia. Blood 117 (25); 6848-55 
  • Sinclair, P.B., Parker, H., An, Q., Rand, V., Ensor, H., Harrison, C.J.* ?, Strefford, J.C.* (2011) Analysis of a breakpoint cluster reveals insight into the mechanism of intrachromosomal amplification in a lymphoid malignancy. Hum Mol Genet 20 (13); 2591-602 
  • Moorman, A.V., Ensor, H.M., Richards, S.M., Chilton, L., Schwab, C., Kinsey, S., Vora, A., Mitchell, C.D., Harrison, C.J.* (2010) The prognostic impact of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia. Lancet Oncology 11 (5); 429-38 
  • Harrison, C.J.?, Hills, R.K., Moorman, A.V., Grimwade, D.J., et al, Webb, D.K.H., Wheatley, K., de Graaf, S.S.N., van den Berg, E., Burnett, A.K., Gibson, B.E.S. (2010) Cytogenetics of childhood acute myeloid leukemia: 729 patients in UK Medical Research Council treatment trials, AML 10 and 12. Journal of Clinical Oncology 28 (16); 2674-81 
  • Russell, L.J., Capasso, M., Vater, I., Akasaka, T., Bernard, O.A., et al, Nguyen-Khac, F., Moorman, A.V., Schwab, C., Dyer, M.J., Siebert, R., Harrison, C.J.*? (2009) Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B cell precursor acute lymphoblastic leukemia. Blood 114 (13); 2688-98. 
  • Russell, L.J., De Castro, D.G., Griffiths, M., Telford, N., Bernard, O., Panzer-Grümayer, R., Heidenreich, O., Moorman, A.V., Harrison, C.J.*? (2009) A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin. Leukemia; 23 (3); 614-617. 
  • Sulong, S., Moorman, A.V., Irving, J.A.E., Strefford, J.C., et al, Bown, N.P., Bailey, S., Hall, A.G. and Harrison, C.J.* (2009) A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukaemia reveals homozygous deletion, haplo-insufficiency, copy number neutral loss of heterozygosity and association with specific cytogenetic subgroups. Blood; 113 (1); 100-107. 
  • Russell, L.J., Akasaka, T., Majid, A., et al, Moorman. A.V., Ross, F., Mazzullo, H., Strefford, J.C., Siebert, R.*, Dyer, M.J.*, Harrison, C.J*?. (2008) t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 111 (1); 387-391 
  • Akasaka, T., Balasas, T., Russell, L.J., Haas, O.A., et al, Strefford, J.C., Harrison, C.J.*?, Siebert, R.*, Dyer, M.J.* (2007). Five members of the CEBP transcription factor family are targeted by recurrent IGH-translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 109 (8); 3451-3461 
  • Moorman, A.V., Richards, S.M., Robinson, H.M., Strefford, J.C., Gibson, B.E., Kinsey, S.E., Eden, O.B., Vora, A.J., Mitchell, C.D, Harrison, CJ.* (2007) Prognosis of children with acute lymphoblastic leukaemia (ALL) and intra-chromosomal amplification of chromosome 21 (iAMP21). Blood 109 (6); 2327-2330.

 

 

Publications