Leukaemia Stem Cell Self-Renewal

Professor Mhairi Copland

Professor of Translational Haematology (Paul O'Gorman Leukaemia Research Centre)

telephone: 01413017881
email: Mhairi.Copland@glasgow.ac.uk

R320 Level 3, Paul O'Gorman Research Centre, Gartnavel General Hospital, Glasgow G12 0YN

Research interests

The Leukaemia Stem Cell Self-Renewal group was established in 2008. Our research group is interested in the abnormalities of stem cell self-renewal and bone marrow microenvironment which develop in myeloid leukaemias. We have specific interests in the Hedgehog pathway in myeloid leukaemias, quiescence as a mechanism of drug resistance in leukaemia stem cells and interactions between leukaemia stem cells and their niche, in particular via the CXCL12/CXCR4 axis. An important aim of our work is the translation of basic laboratory research to clinical trials which we have achieved with the use of Hedgehog pathway inhibitors in chronic myeloid leukaemia.

Research interests

Aberrant leukaemia stem cell self-renewal and altered bone marrow microenvironment or “niche” allows the leukaemia stem cells to survive the most effective chemotherapeutic strategies available today, resulting in refractory leukaemia or relapse. Small molecule inhibitors are increasingly becoming available to target these essential stem cell pathways and assessing these novel compounds forms a very important part of our research.

We use a combination of immunomagentic cell separation and multi-parameter fluorescence activated cell sorting (FACS) to isolate the most primitive haemopoietic stem cells from the progenitor cells in both normal and leukaemic primary samples. We then use a combination of long and short-term culture techniques, together with a number of gene expression (microarray, Taqman qRT-PCR, Fluidigm) and protein expression/activity (Western blotting, flow cytometry, immunofluorescence) approaches to assess the differences between normal and leukaemic cells and the effects of small molecule inhibitors. In addition, we are currently involved with extending the leukaemia Biobank to include samples from patients with acute leukaemia and myelodysplastic syndrome.

We work with several academic collaborators including Professor Jon Cooper (Glasgow), Professor Peter Adams (Glasgow), Dr David Vetrie (Glasgow), Dr Kathryn Ball (Edinburgh), Professor Junia Melo (Adelaide) and Dr Ravi Bhatia (Duarte). We currently have industrial collaborations with Novartis, Genzyme and Bristol-Myers Squibb.

Individual projects:

• An investigation of the control of cell division and quiescence in leukaemic versus normal haemopoietic stem and progenitor cell
• Phase 1 clinical trial “Dasatinib (BMS-354825) combined with SMO inhibitor (BMS-833923; XL139) in CML either resistant to imatinib or nilotinib or with suboptimal response to any prior TKI
• Development of a biomarker assay for the assessment of Hedgehog pathway activity in hematological malignancies
• Hedgehog signalling as a leukaemia stem cell self-renewal pathway in CML.
• Antagonising the CXCR4/SDF-1 interaction in chronic myeloid leukaemia for sensitisation to tyrosine kinase inhibitors

Publications

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Number of items: 102.

2024

Copland, M. (2024) Triplet therapy for advanced BCR::ABL1 positive myeloid leukaemias. Lancet Haematology, (doi: 10.1016/S2352-3026(24)00282-5) (In Press)

Khalaf, A. et al. (2024) Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia. Science Translational Medicine, 16(751), eadi5336. (doi: 10.1126/scitranslmed.adi5336) (PMID:38865484)

Zarou, M. M. et al. (2024) Inhibition of mitochondrial folate metabolism drives differentiation through mTORC1-mediated purine sensing. Nature Communications, 15, 1931. (doi: 10.1038/s41467-024-46114-0) (PMID:38431691) (PMCID:PMC10908830)

Copland, M. et al. (2024) A randomised evaluation of low-dose cytosine arabinoside plus lenalidomide versus single-agent low-dose cytosine arabinoside in older patients with acute myeloid leukaemia: Results from the LI-1 trial. British Journal of Haematology, 204(3), (doi: 10.1111/bjh.19220) (PMID:38016651)

Dawson, A. et al. (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15, 1090. (doi: 10.1038/s41467-024-45471-0) (PMID:38316788) (PMCID:PMC10844594)

Scott, M. T. et al. (2024) Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease. Nature Communications, 15, 651. (doi: 10.1038/s41467-024-44771-9) (PMID:38246924) (PMCID:PMC10800356)

2023

Zarou, M. M. et al. (2023) Leukaemia Exposure Alters the Transcriptional Profile and Function of Macrophages in the Bone Marrow Niche. 65th ASH Annual Meeting and Exposition, San Diego, California, USA, 09-12 Dec 2023. (doi: 10.1182/blood-2023-181630)

Rattigan, K. M. et al. (2023) Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells. EMBO Reports, 24, e56279. (doi: 10.15252/embr.202256279) (PMID:37489735) (PMCID:PMC10561355)

Rattigan, K. M. et al. (2023) Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells. Nature Communications, 14, 4634. (doi: 10.1038/s41467-023-40222-z) (PMID:37591854) (PMCID:PMC10435520)

Fernando, F., Innes, A. J., Claudiani, S., Pryce, A., Hayden, C., Byrne, J., Gallipoli, P., Copland, M. , Apperley, J. F. and Milojkovic, D. (2023) The outcome of post-transplant asciminib in patients with chronic myeloid leukaemia. Bone Marrow Transplantation, 58(7), pp. 826-828. (doi: 10.1038/s41409-023-01975-9) (PMID:37015970)

Patterson, S. D. and Copland, M. (2023) The bone marrow immune microenvironment in CML: treatment responses, treatment-free remission, and therapeutic vulnerabilities. Current Hematologic Malignancy Reports, 18(2), pp. 19-32. (doi: 10.1007/s11899-023-00688-6) (PMID:36780103) (PMCID:PMC9995533)

Leak, S., Horne, G. and Copland, M. (2023) Targeting BCR-ABL1-positive leukaemias, a review article. Cambridge Prisms: Precision Medicine, 1, e21. (doi: 10.1017/pcm.2023.9)

Mussai, F. et al. (2023) A randomised evaluation of low-dose Ara-C plus pegylated recombinant arginase BCT-100 versus low dose Ara-C in older unfit patients with acute myeloid leukaemia: results from the LI-1 trial. British Journal of Haematology, 200(5), pp. 573-578. (doi: 10.1111/bjh.18560) (PMID:36413792)

Mehta, P., Telford, N., Wragg, C., Dillon, R., Freeman, S., Finnegan, D., Hamblin, A., Copland, M. and Knapper, S. (2023) A British Society for Haematology good practice paper: Recommendations for laboratory testing of UK patients with acute myeloid leukaemia. British Journal of Haematology, 200(2), pp. 150-159. (doi: 10.1111/bjh.18516) (PMID:36278472)

2022

Copland, M. (2022) Treatment of blast phase chronic myeloid leukaemia: a rare and challenging entity. British Journal of Haematology, 199(5), pp. 665-678. (doi: 10.1111/bjh.18370) (PMID:35866251)

Parry, N., Busch, C., Aßmann, V., Cassels, J., Hair, A., Helgason, G. V. , Wheadon, H. and Copland, M. (2022) BH3 mimetics in combination with nilotinib or ponatinib represent a promising therapeutic strategy in blast phase chronic myeloid leukemia. Cell Death Discovery, 8, 457. (doi: 10.1038/s41420-022-01211-1) (PMID:36379918) (PMCID:PMC9666353)

Gómez-Castañeda, E., Hopcroft, L. E.M. , Rogers, S. , Munje, C., Bittencourt-Silvestre, J., Copland, M. , Vetrie, D. , Holyoake, T. and Jørgensen, H. G. (2022) Tyrosine kinase inhibitor independent gene expression signature in CML offers new targets for LSPC eradication therapy. Cancers, 14(21), 5253. (doi: 10.3390/cancers14215253) (PMID:36358672) (PMCID:PMC9655972)

Dennis, M. et al. (2022) Management of older patients with frailty and acute myeloid leukaemia: a British Society for Haematology good practice paper. British Journal of Haematology, 199(2), pp. 205-221. (doi: 10.1111/bjh.18369) (PMID:36000944)

Lebecque, B. et al. (2022) The spliceosome: a new therapeutic target in chronic myeloid leukaemia. Cancers, 14(19), 4695. (doi: 10.3390/cancers14194695) (PMID:36230624) (PMCID:PMC9563771)

Robertson, N. A. et al. (2022) Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects. Nature Medicine, 28(7), pp. 1439-1446. (doi: 10.1038/s41591-022-01883-3) (PMID:35788175) (PMCID:PMC9307482)

Marks, D. I. et al. (2022) In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial. Lancet Haematology, 9(4), e276-e288. (doi: 10.1016/S2352-3026(22)00036-9) (PMID:35358442) (PMCID:PMC8969058)

Copland, M. et al. (2022) Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial. Lancet Haematology, 9(2), e121-e132. (doi: 10.1016/S2352-3026(21)00370-7) (PMID:34906334)

Love, S. B. et al. (2022) Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units. Trials, 23, 757. (doi: 10.1186/s13063-022-06680-4) (PMID:36068599) (PMCID:PMC9449272)

2021

Dennis, M. et al. (2021) Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients. Blood Advances, 5(24), pp. 5621-5625. (doi: 10.1182/bloodadvances.2021005038) (PMID:34597366) (PMCID:PMC8714727)

Ianniciello, A. et al. (2021) ULK1 inhibition promotes oxidative stress–induced differentiation and sensitizes leukemic stem cells to targeted therapy. Science Translational Medicine, 13(613), eabd5016. (doi: 10.1126/scitranslmed.abd5016) (PMID:34586834)

Chantkran, W., Hsieh, Y.-C., Zheleva, D., Frame, S., Wheadon, H. and Copland, M. (2021) Interrogation of novel CDK2/9 inhibitor fadraciclib (CYC065) as a potential therapeutic approach for AML. Cell Death Discovery, 7, 137. (doi: 10.1038/s41420-021-00496-y) (PMID:34112754) (PMCID:PMC8192769)

Hsieh, Y.-C., Kirschner, K. and Copland, M. (2021) Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia, 35(5), pp. 1229-1242. (doi: 10.1038/s41375-021-01238-w) (PMID:33833387) (PMCID:PMC8102187)

Mooney, L., Goodyear, C. S. , Chandra, T., Kirschner, K. , Copland, M. , Petrie, M. C. and Lang, N. N. (2021) Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure. Clinical Science, 135(7), pp. 991-1007. (doi: 10.1042/CS20200306) (PMID:33861346) (PMCID:PMC8055963)

Latif, A.-L. et al. (2021) BRD4-mediated repression of p53 is a target for combination therapy in AML. Nature Communications, 12, 241. (doi: 10.1038/s41467-020-20378-8) (PMID:33431824) (PMCID:PMC7801601)

Parry, N., Wheadon, H. and Copland, M. (2021) The application of BH3 mimetics in myeloid leukemias. Cell Death and Disease, 12, 222. (doi: 10.1038/s41419-021-03500-6) (PMID:33637708) (PMCID:PMC7908010)

2020

Horne, G. et al. (2020) A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease. Leukemia, 34(7), pp. 1775-1786. (doi: 10.1038/s41375-019-0700-9) (PMID:31925317) (PMCID:PMC7224085)

Kinstrie, R. et al. (2020) CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy. Leukemia, 34(6), pp. 1613-1625. (doi: 10.1038/s41375-019-0684-5) (PMID:31896780) (PMCID:PMC7272220)

Vetrie, D. , Helgason, V. and Copland, M. (2020) The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML. Nature Reviews Cancer, 20, pp. 158-173. (doi: 10.1038/s41568-019-0230-9) (PMID:31907378)

2019

Claudiani, S. et al. (2019) Introducing a predictive score for successful treatment free remission in chronic myeloid leukemia (CML). Blood, 134(Sup_1), p. 26. (doi: 10.1182/blood-2019-131500)

Copland, M. (2019) Is there a role for dose modification of TKI therapy in CML. Current Hematologic Malignancy Reports, 14(4), pp. 337-345. (doi: 10.1007/s11899-019-00524-w) (PMID:31197525) (PMCID:PMC6647386)

Clark, R. E. et al. (2019) De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. Lancet Haematology, 6(7), e375-e383. (doi: 10.1016/S2352-3026(19)30094-8) (PMID:31201085)

Mitchell, R. and Copland, M. (2019) Defining niche interactions to target chronic myeloid leukemia stem cells. Haematologica, 105(1), pp. 2-4. (doi: 10.3324/haematol.2019.234898) (PMID:31894093) (PMCID:PMC6939514)

2018

Toofan, P., Busch, C., Morrison, H., O'Brien, S., Jørgensen, H. , Copland, M. and Wheadon, H. (2018) Chronic myeloid leukemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal. Cell Death and Disease, 9, 927. (doi: 10.1038/s41419-018-0905-2) (PMID:30206237) (PMCID:PMC6134087)

Cross, N. C.P., White, H. W., Evans, P. A.S., Hancock, J., Copland, M. , Milojkovic, D., Mason, J., Craine, S. and Mead, A. J. (2018) Consensus on BCR-ABL1 reporting in chronic myeloid leukaemia in the UK. British Journal of Haematology, 182(6), pp. 777-788. (doi: 10.1111/bjh.15542) (PMID:30125955) (PMCID:PMC6175193)

Zhang, B. et al. (2018) Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia. Nature Medicine, 24, pp. 450-462. (doi: 10.1038/nm.4499) (PMID:29505034) (PMCID:PMC5965294)

Munje, C. and Copland, M. (2018) Exploring stem cell heterogeneity in chronic myeloid leukemia. Trends in Cancer, 4(3), pp. 167-169. (doi: 10.1016/j.trecan.2017.12.001) (PMID:29506666)

2017

Lewis, M., Copland, M. , Soverini, S., Sadovnik, I., Bedel, A., Prost, S., Italiano, A. and Mahon, F.-X. (2017) What are the challenges in 2016 regarding resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and cancer? Hematological Oncology, 35(4), pp. 420-423. (doi: 10.1002/hon.2329) (PMID:27435333)

Brock, K., Billingham, L., Copland, M. , Siddique, S., Sirovica, M. and Yap, C. (2017) Implementing the EffTox dose-finding design in the Matchpoint trial. BMC Medical Research Methodology, 17, 112. (doi: 10.1186/s12874-017-0381-x) (PMID:28728594) (PMCID:PMC5520236)

Clark, R. E. et al. (2017) De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematology, 4(7), e310-e316. (doi: 10.1016/S2352-3026(17)30066-2) (PMID:28566209)

Horne, G. A. and Copland, M. (2017) Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments. Expert Opinion on Drug Discovery, 12(5), pp. 465-474. (doi: 10.1080/17460441.2017.1303477) (PMID:28277836)

2016

Kinstrie, R., Karamitros, D., Goardon, N., Morrison, H., Hamblin, M., Robinson, L., Clark, R. E., Copland, M. and Vyas, P. (2016) Heterogeneous leukemia stem cells in myeloid blast phase chronic myeloid leukemia. Blood Advances, 1(3), pp. 160-169. (doi: 10.1182/bloodadvances.2016000810)

Horne, G. A. , Morrison, H., Campbell, V., Kinstrie, R., Cassels, J., Hair, A., Vetrie, D. , Wheadon, H. , Holyoake, T. L. and Copland, M. (2016) Notch Pathway Activation Targets Leukemic Stem Cells in Chronic-Phase Chronic Myeloid Leukemia (CP-CML). American Society of Hematology 58th Annual Meeting, San Diego, CA, USA, 3-6 Dec 2016.

Abraham, S. A. et al. (2016) Dual targeting of P53 and C-MYC induces selective elimination of leukemic stem cells. Nature, 534(7607), pp. 341-346. (doi: 10.1038/nature18288) (PMID:27281222) (PMCID:PMC4913876)

Gómez-Castañeda, E., Hopcroft, L.E.M. , Rogers, S. , Jorgensen, H.G. , Pellicano, F., Vetrie, D. , Copland, M. , Grimmond, S. and Holyoake, T.L. (2016) Uncovering the BCR-ABL1 Tyrosine Kinase Independent Signature in Chronic Myeloid Leukaemia Stem Cells. 36th World Congress of the International Society of Hematology, Glasgow, Scotland, 18-21 Apr 2016. (doi: 10.1111/bjh.14019)

Irvine, D. A. et al. (2016) Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Scientific Reports, 6, 25476. (doi: 10.1038/srep25476) (PMID:27157927) (PMCID:PMC4860619)

Brehme, M., Koschmieder, S., Montazeri, M., Copland, M. , Oehler, V. G., Radich, J. P., Brümmendorf, T. H., and Schuppert, A. (2016) Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia. Scientific Reports, 6, 24057. (doi: 10.1038/srep24057) (PMID:27048866) (PMCID:PMC4822142)

Schemionek, M. et al. (2016) MTSS1 is a critical epigenetically regulated tumor suppressor in CML. Leukemia, 30(4), pp. 823-830. (doi: 10.1038/leu.2015.329) (PMID:26621336)

2015

Latif, A.-L., Cole, J. J., Monteiro Campos, J., Clark, W., McGarry, L., Brock, C., Newcombe, A., Keeshan, K. , Copland, M. and Adams, P. D. (2015) Dual inhibition of MDM2 and BET cooperate to eradicate acute myeloid leukemia. Blood, 126(23), p. 674. (doi: 10.1182/blood.V126.23.674.674)

Horne, G. A. , Kinstrie, R. and Copland, M. (2015) Novel drug therapies in myelois leukemia: a patent review. Pharmaceutical Patent Analyst, 4(3), pp. 187-205. (doi: 10.4155/ppa.15.3) (PMID:26030080)

2014

Lund, K., Cole, J., VanderKraats, N. D., McBryan, T., Pchelintsev, N. A., Clark, W., Copland, M. , Edwards, J. R. and Adams, P. (2014) DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML. Genome Biology, 15(7), p. 406. (doi: 10.1186/s13059-014-0406-2)

Burt, C., Parker, A., McQuaker, G., Copland, M. , Brierley, C., Little, A. and Clark, A. (2014) In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors. Bone Marrow Transplantation, 49(5), pp. 657-663. (doi: 10.1038/bmt.2014.8)

Lund, K., Cole, J., McBryan, T., Copland, M. and Adams, P. (2014) Investigating effects of epigenetic modulation in acute myeloid leukaemia. Lancet, 383(Supl 1), S70. (doi: 10.1016/S0140-6736(14)60333-0) (PMID:19345831) (PMCID:PMC2866651)

Braig, M. et al. (2014) A 'telomere-associated secretory phenotype' cooperates with BCR-ABL to drive malignant proliferation of leukemic cells. Leukemia, 28(10), pp. 2028-2039. (doi: 10.1038/leu.2014.95) (PMID:24603533)

Lund, K., Adams, P.D. and Copland, M. (2014) EZH2 in normal and malignant hematopoiesis. Leukemia, 28(1), pp. 44-49. (doi: 10.1038/leu.2013.288) (PMID:24097338)

Pellicano, F. et al. (2014) The antiproliferative activity of kinase inhibitors in chronic myeloid leukemia cells is mediated by FOXO transcription factors. Stem Cells, 32(9), pp. 2324-2337. (doi: 10.1002/stem.1748) (PMID:24806995) (PMCID:PMC4282530)

Toofan, P., Irvine, D., Hopcroft, L. , Copland, M. and Wheadon, H. (2014) The role of the bone morphogenetic proteins in leukaemic stem cell persistence. Biochemical Society Transactions, 42(4), pp. 809-815. (doi: 10.1042/BST20140037)

2013

Gallipoli, P., Pellicano, F., Morrison, H., Laidlaw, K., Allan, E.K., Bhatia, R., Copland, M. , Jorgensen, H.G. and Holyoake, T.L. (2013) Autocrine TNF-α production supports CML stem and progenitor cell survival and enhances their proliferation. Blood, 122(19), pp. 3335-3339. (doi: 10.1182/blood-2013-02-485607) (PMID:24041577) (PMCID:PMC3953090)

Valent, P., Bonnet, D., Wohrer, S., Andreeff, M., Copland, M., , Chomienne, C. and Eaves, C. (2013) Heterogeneity of neoplastic stem cells: theoretical, functional, and clinical implications. Cancer Research, 73(3), pp. 1037-1045. (doi: 10.1158/0008-5472.CAN-12-3678)

Balabanov, S., Evans, C.A., Abraham, S.A., Pellicano, F., Copland, M. , Walker, M.J., Whetton, A.D. and Holyoake, T.L. (2013) Quantitative proteomics analysis of BMS-214662 effects on CD34 positive cells from chronic myeloid leukaemia patients. Proteomics, 13(1), pp. 153-168. (doi: 10.1002/pmic.201200022)

Cramer-Morales, K. et al. (2013) Personalized synthetic lethality induced by targeting RAD52 in leukemias identified by gene mutation and expression profile. Blood, 122(7), pp. 1293-1304. (doi: 10.1182/blood-2013-05-501072)

Rhodes, S. , Copland, M. , Hopcroft, L. , Sayeski, P. and Wheadon, H. (2013) Identification of JAK2 dependent transcriptional regulators in CML. In: 42nd Annual Scientific Meeting of the ISEH – Society for Hematology and Stem Cells, Vienna, Austria, 22-25 Aug 2013, S47-S47.

Sands, W.A., Copland, M. and Wheadon, H. (2013) Targeting self-renewal pathways in myeloid malignancies. Cell Communication and Signaling, 11(33), (doi: 10.1186/1478-811X-11-33)

2012

Kinstrie, R. and Copland, M. (2012) Targeting chronic myeloid leukemia stem cells. Current Hematologic Malignancy Reports, 8(1), pp. 14-21. (doi: 10.1007/s11899-012-0148-8) (PMID:23264204)

Flis, K., Irvine, D., Copland, M. , Bhatia, R. and Skorski, T. (2012) Chronic myeloid leukemia stem cells display alterations in expression of genes involved in oxidative phosphorylation. Leukemia and Lymphoma, 53(12), pp. 2474-2478. (doi: 10.3109/10428194.2012.696313)

Eyre, T. et al. (2012) Episomal amplification of NUP214-ABL1 fusion gene in B-cell acute lymphoblastic leukemia. Blood, 120(22), pp. 4441-4443. (doi: 10.1182/blood-2012-09-456517)

Valent, P. et al. (2012) Cancer stem cell definitions and terminology: the devil is in the details. Nature Reviews Cancer, 12(11), pp. 767-775. (doi: 10.1038/nrc3368)

Rodgers, R., Latif, Z. and Copland, M. (2012) How I manage priapism in chronic myeloid leukaemia patients. British Journal of Haematology, 158(2), pp. 155-164. (doi: 10.1111/j.1365-2141.2012.09151.x)

Faley, S., Copland, M. , Reboud, J. and Cooper, J. M. (2012) Intracellular protein trafficking kinetics in chronic myeloid leukemia stem cells using a microfluidic platform. Integrative Biology, 4(4), p. 368. (doi: 10.1039/c2ib00086e)

Irvine, D.A. and Copland, M. (2012) Targeting hedgehog in hematologic malignancy. Blood, 119(10), pp. 2196-2204. (doi: 10.1182/blood-2011-10-383752)

2011

Pellicano, F., Simara, P., Sinclair, A., Helgason, G.V. , Copland, M. , Grant, S. and Holyoake, T.L. (2011) The MEK inhibitor PD184352 enhances BMS-214662-induced apoptosis in CD34+ CML stem/progenitor cells. Leukemia, 25(7), pp. 1159-67. (doi: 10.1038/leu.2011.67)

Lucas, C. M., Harris, R. J., Giannoudis, A., Copland, M. , Slupsky, J. R. and Clark, R. E. (2011) Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood, 117(24), pp. 6660-6668. (doi: 10.1182/blood-2010-08-304477)

Faley, S.L., Copland, M. , Reboud, J. and Cooper, J.M. (2011) Cell chip array for microfluidic proteomics enabling rapid in situ assessment of intracellular protein phosphorylation. Biomicrofluidics, 5(2), 024106. (doi: 10.1063/1.3587095)

2009

Pellicano, F., Copland, M. , Jorgensen, H. G. , Mountford, J., Leber, B. and Holyoake, T. L. (2009) BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34⁺38^- cells, through activation of protein kinase Cβ. Blood, 114(19), pp. 4186-4196. (doi: 10.1182/blood-2009-05-219550)

Faley, S. L., Copland, M. , Wlodkowic, D., Kolch, W., Seale, K. T., Wikswo, J. P. and Cooper, J. M. (2009) Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab on a Chip, 9(18), pp. 2659-2664. (doi: 10.1039/b902083g)

Copland, M. (2009) Ikaros deletions are associated with poor prognosis in acute lymphoblastic leukemia. Future Oncology, 5(4), pp. 455-458. (doi: 10.2217/FON.09.16)

Copland, M. (2009) Chronic myelogenous leukemia stem cells: what's new? Current Hematologic Malignancy Reports, 4(2), pp. 66-73. (doi: 10.1007/s11899-009-0010-9)

Copland, M. , Michie, A. M. and Holyoake, T. L. (2009) Stem cells in Leukemia and other hematological malignancies. In: Majumder, S. (ed.) Stem Cells and Cancer. Springer New York: New York, NY, pp. 111-136. ISBN 9780387896106 (doi: 10.1007/978-0-387-89611-3_5)

Faley, S.L., Copland, M. , Wlodkovic, D., Kolch, W., Seale, K.T., Wikswo, J.P. and Cooper, J. (2009) Pachinko Biology: Gambling on Single Cells. In: 2009 35th Annual Northeast Bioengineering Conference. IEEE: New York, pp. 15-17. ISBN 978-1-4244-4362-8

2008

Konig, H., Copland, M., Chu, S., Jove, R., Holyoake, T. L. and Bhatia, R. (2008) Effects of Dasatinib on Src Kinase Activity and Downstream Intracellular Signaling in Primitive Chronic Myelogenous Leukemia Hematopoietic Cells. Cancer Research, 68(23), pp. 9624-9633. (doi: 10.1158/0008-5472.CAN-08-1131)

Heaney, N. B., Copland, M., Stewart, K., Godden, J., Parker, A. N., McQuaker, I. G., Smith, G. M., Crawley, C., Shepherd, P. and Holyoake, T. L. (2008) Complete molecular responses are achieved after reduced intensity stem cell transplantation and donor lymphocyte infusion in chronic myeloid leukemia. Blood, 111(10), pp. 5252-5255. (doi: 10.1182/blood-2007-10-118141)

Copland, M., Pellicano, F., Richmond, L., Allan, E. K., Hamilton, A., Lee, F. Y., Weinmann, R. and Holyoake, T. L. (2008) BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors. Blood, 111(5), pp. 2843-2853. (doi: 10.1182/blood-2007-09-112573)

2007

Holyoake, T. and Copland, M. (2007) LSC defenses breached by chemical arsenal. Blood, 110(13), pp. 4138-4139.

Balabanov, S. et al. (2007) Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL-positive leukemias identified by a proteomics approach. Blood, 109(4), pp. 1701-1711. (doi: 10.1182/blood-2005-03-037648)

Copland, M. , Hamilton, A. and Holyoake, T. (2007) Conventional Western blotting techniques will not reliably quantify p210 BCR-ABL - Response. Blood, 109(3), p. 1336. (doi: 10.1182/blood-2006-11-054031)

Konig, H., Copland, M. , Jove, R., Holyoake, T. and Bhatia, R. (2007) Effect of dasatinib on BCR-ABL and Src mediated growth signaling in primary CML hematopoietic progenitors. Blood, 110(11), 865A-865A.

2006

Copland, M., Hamilton, A., Eirick, L., Baird, J., Allan, E., Jordanides, N., Barow, M., Mountford, J. and Holyoake, T. (2006) Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood, 107(11), pp. 4532-4539. (doi: 10.1182/blood-2005-07-2947)

Hamilton, A., Elrick, L., Myssina, S., Copland, M. , Jorgensen, H.G. , Melo, J.V. and Holyoake, T.L. (2006) BCR-ABL activity and its response to drugs can be determined in CD34⁺ CML stem cells by CrkL phosphorylation status using flow cytometry. Leukemia, 20(6), pp. 1035-1039. (doi: 10.1038/sj.leu.2404189)

Jorgensen, H.G. , Copland, M. , Allan, E.K., Jiang, X.Y., Eaves, A., Eaves, C. and Holyoake, T.L. (2006) Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clinical Cancer Research, 12(2), pp. 626-633. (doi: 10.1158/1078-0432.CCR-05-0429)

2005

Copland, M. , Jorgensen, H.G. and Holyoake, T.L. (2005) Evolving molecular therapy for chronic myeloid leukaemia - are we on target? Hematology, 10(5), pp. 349-359. (doi: 10.1080/10245330500234195)

Copland, M., Fraser, A., Harrison, S. and Holyoake, T. (2005) Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia. Cancer Immunology Immunotherapy, 54(4), pp. 297-306. (doi: 10.1007/s00262-004-0573-1)

Allan, E., Jordanides, N., McLintock, L., Copland, M., Devaney, M., Stewart, K., Parker, A., Johnson, P., Holyoake, T. and Jones, B. (2005) Poor performance of galactomannan and mannan sandwich enzyme-linked immunosorbent assays in the diagnosis of invasive fungal infection. British Journal of Haematology, 128(4), pp. 578-579. (doi: 10.1111/j.1365-2141.2004.05333.x)

Jordanides, N., Allan, E., McLintock, L., Copland, M., Devaney, M., Stewart, K., Parker, A., Johnson, P., Holyoake, T. and Jones, B. (2005) A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients. Bone Marrow Transplantation, 35(4), pp. 389-395. (doi: 10.1038/sj.bmt.1704768)

Jorgensen, H.G. , Copland, M. and Holyoake, T. (2005) Granulocyte-colony-stimulating factor (filgrastim) may overcome imatinib-induced neutropenia in patients with chronic-phase myelogenous leukemia. Cancer, 103(1), pp. 210-211. (doi: 10.1002/cncr.20742)

Copland, M. , Hamilton, A., Baird, J., Barow, M., Allan, E., Elrick, L. and Holyoake, T. (2005) Dasatinib (BMS-354825) has increased activity against Bcr-Abl compared to imatinib in primary CML cells in vitro, but does not eradicate quiescent CML stem cells. Blood, 106(11), 205A-205A.

2004

McLintock, L., Jordanides, N., Allan, E., Copland, M., Stewart, K., Parker, A., Devaney, M., Holyoake, T. and Jones, B. (2004) The use of a risk group stratification in the management of invasive fungal infection: a prospective validation. British Journal of Haematology, 124(3), pp. 403-404. (doi: 10.1046/j.1365-2141.2003.04794.x)

2003

Kilpatrick, D.C. et al. (2003) No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections. Clinical and Experimental Immunology, 134(2), pp. 279-284. (doi: 10.1046/j.1365-2249.2003.02284.x)

2001

Copland, M. , Walker, I.D. and Tait, R.C. (2001) Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation. Archives of Internal Medicine, 161(17), pp. 2125-2128. (doi: 10.1001/archinte.161.17.2125)

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