Research Institute in Oncology and Hematology

James Johnston

Chronic Lymphocytic Leukemia

Contact: Dr James Johnston MB, BCh, FRCPC
Research Institute in Oncology and Hematology
2078-675 McDermot Ave
Winnipeg, Mb R3E 0V9
Email: Dr James Johnston MB, BCh, FRCPC

Chronic Lymphocytic Leukemia

My primary research interest is in chronic lymphocytic leukemia (CLL) and I am involved in a number of translational research programs related to this disease. These studies involve the epidemiology and basic science of CLL, in addition to clinical trials. To further these activities, we have developed the CLL Clinic at CancerCare Manitoba and the Manitoba CLL Tumour Bank, which is housed in the MICB. Our epidemiological studies have demonstrated that the incidence of CLL is much higher than previously reported with elderly male patients having a particularly poor prognosis. Our ongoing laboratory studies are evaluating new therapies and prognostic markers in CLL and examining the effects of age and gender on the biology of this cancer.

Team Members

  • Sara Kost (Technician)
  • Lin Yang (Medical Fellow)

Publications since 2010

PubMed Listed Publications
  1. Comparison of outcome of patients with CLL who are referred or nonreferred to a specialized CLL clinic: a Canadian population-based study. Beiggi S, Banerji V, Deneka A, Griffith J, Gibson SB, Johnston JB.. Cancer Med. 2016 Jun;5(6):971-9. doi: 10.1002/cam4.559. Epub 2016 Feb 18.
  2. Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism. Dielschneider RF, Eisenstat H, Mi S, Curtis JM, Xiao W, Johnston JB., Gibson SB. Leukemia. 2016 Jun;30(6):1290-300. doi: 10.1038/leu.2016.4. Epub 2015 Feb 23.
  3. Li H, Wu X, Hou S, Malek M, Kielkowska A, Noh E, Makondo KJ, Du Q, Wilkins JA, Johnston JB., Gibson SB, Lin F, Marshall AJ. Phosphatidylinositol-3,4-Bisphosphate and Its Binding Protein Lamellipodin Regulate Chemotaxis of Malignant B Lymphocytes. J Immunol. 2016 Jan 15;196(2):586-95. doi: 10.4049/jimmunol.1500630. Epub 2015 Dec 22.
  4. Quest GR, Johnston JB. Clinical features and diagnosis of hairy cell leukemia. Best Pract Res Clin Haematol. 2015 Dec;28(4):180-92. doi: 10.1016/j.beha.2015.10.017. Epub 2015 Oct 26. Review.
  5. Ye X, Mneina A, Johnston JB., Mahmud SM. Associations between statin use and non-Hodgkin lymphoma (NHL) risk and survival: a meta-analysis. Hematol Oncol. 2015 Oct 20. doi: 10.1002/hon.2265. [Epub ahead of print]
  6. Johnston JB.Enhancing monoclonal antibody activity in chronic lymphocytic leukemia. Leuk Lymphoma. 2015 Sep 18:1-2. [Epub ahead of print] No abstract available.
  7. Lafarge ST, Hou S, Pauls SD, Johnston JB, Gibson SB, Marshall AJ. Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70. Leuk Res. 2015 Jul;39(7):773-8. doi: 10.1016/j.leukres.2015.04.016. Epub 2015 May 2.
  8. Kriangkum J, Motz SN, Mack T, Beiggi S, Baigorri E, Kuppusamy H, Belch AR, Johnston JB, Pilarski LM. Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia. PLoS One. 2015 Sep 9;10(9):e0137232. doi: 10.1371/journal.pone.0137232. eCollection 2015
  9. Kouroukis CT, Crump M, MacDonald D, Larouche JF, Stewart D, Johnston JB, Sauvageau S, Beausoleil E, Sage P, Dubois S, Christofides A, Di Clemente S, and Sehn L. An open-label expanded access trial for bendamustine in patients with refractory iNHL or previously untreated CLL (BEND-ACT). Current Oncology 2015 Aug;22(4):e260-71.
  10. Lafarge ST, Li H, Pauls SD, Hou S, Johnston JB, Gibson SB, Marshall AJ. ZAP70 expression directly promotes chronic lymphocytic leukaemia cell adhesion to bone marrow stromal cells. Br J Haematol. 2015 Jan;168(1):139-42. doi: 10.1111/bjh.13063. Epub 2014 Aug 4. No abstract available.
  11. Beauchemin C, Johnston JB, Lapierre MÈ, Aissa F, Lachaine J. Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis. Curr Oncol. 2015 Jun;22(3):e148-56. doi: 10.3747/co.22.2119.
  12. Gehrke I, Bouchard ED, Beiggi S, Poeppl AG, Johnston JB, Gibson SB, Banerji V. On-target effect of FK866, a nicotinamide phosphoribosyl transferase inhibitor, by apoptosis-mediated death in chronic lymphocytic leukemia cells.Clin Cancer Res. 2014 Sep 15;20(18):4861-72. doi: 10.1158/1078-0432.CCR-14-0624. Epub 2014 Aug 29.
  13. Dielschneider RF, Xiao W, Yoon JY, Noh E, Banerji V, Li H, Marshall AJ, Johnston JB, Gibson SB. Gefitinib targets ZAP-70-expressing chronic lymphocytic leukemia cells and inhibits B-cell receptor signaling. Cell Death Dis. 2014 Oct 2;5:e1439. doi: 10.1038/cddis.2014.391.
  14. Minuk GY, Lerner B, Gibson SB, Johnston JB, Uhanova J, Andonov A, Wu J. Hepatitis B and hepatitis C viral infections in patients with chronic lymphocytic leukemia. Can J Gastroenterol Hepatol. 2014 Mar;28(3):131-4.
  15. Yoon JY, Ishdorj G, Graham BA, Johnston JB, Gibson SB. Valproic acid enhances fludarabine-induced apoptosis mediated by ROS and involving decreased AKT and ATM activation in B-cell-lymphoid neoplastic cells.Apoptosis. 2014 Jan;19(1):191-200. doi: 10.1007/s10495-013-0906-7.
  16. Lafarge ST, Johnston JB, Gibson SB, Marshall AJ. Adhesion of ZAP-70+ chronic lymphocytic leukemia cells to stromal cells is enhanced by cytokines and blocked by inhibitors of the PI3-kinase pathway.Leuk Res. 2014 Jan;38(1):109-15. doi: 10.1016/j.leukres.2013.08.001. Epub 2013 Aug 9.
  17. Kuppusamy H, Ogmundsdottir HM, Baigorri E, Warkentin A, Steingrimsdottir H, Haraldsdottir V, Mant MJ, Mackey J, Johnston JB Adamia S, Belch AR, Pilarski LM. Inherited polymorphisms in hyaluronan synthase 1 predict risk of systemic B-cell malignancies but not of breast cancer.PLoS One. 2014 Jun 20;9(6):e100691. doi: 10.1371/journal.pone.0100691. eCollection 2014.
  18. Yoon JY, Szwajcer D, Ishdorj G, Benjaminson P, Xiao W, Kumar R,Johnston JB, Gibson SB. Synergistic apoptotic response between valproic acid and fludarabine in chronic lymphocytic leukaemia (CLL) cells involves the lysosomal protease cathepsin B.Blood Cancer J. 2013 Oct 18;3:e153. doi: 10.1038/bcj.2013.50.
  19. Beiggi S, Johnston JB, Seftel MD, Pitz MW, Kumar R, Banerji V, J Griffith E, Gibson SB. Increased risk of second malignancies in chronic lymphocytic leukaemia patients as compared with follicular lymphoma patients: a Canadian population-based study. Br J Cancer. 2013 Jul 16. doi: 10.1038/bjc.2013.381. [Epub ahead of print]
  20. Kriangkum J, Motz SN, Debes Marun CS, Lafarge ST, Gibson SB, Venner CP, Johnston JB, Belch AR, Pilarski LM. Frequent occurrence of highly expanded but unrelated B-cell clones in patients with multiple myeloma. PLoS One. 2013 May 28;8(5):e64927. doi: 10.1371/journal.pone.0064927. Print 2013.
  21. Johnston JB. Jump-starting the T cells in CLL. Blood. 2013 May 16;121(20):4016-7. doi: 10.1182/blood-2013-04-491787.
  22. Yoon JY, Lafarge S, Dawe D, Lakhi S, Kumar R, Morales C, Marshall A, Gibson SB, Johnston JB.Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia.Leuk Lymphoma. 2012 Sep;53(9):1735-42.
  23. Yoon JY, Kumar R, Aloyz R, Johnston JB. Response of concomitant chronic myelogenous leukemia and chronic lymphocytic leukemia to imatinib mesylate. Leuk Res. 2011 Sep;35(9):e179-80.
  24. Ishdorj G, Johnston JB, Gibson SB. Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B leukemic cells. BMC Cancer. 2011 Jun 24;11:268.
  25. Xiao W, Ishdorj G, Sun J, Johnston JB, Gibson SB. Death receptor 4 is preferentially recruited to lipid rafts in chronic lymphocytic leukemia cells contributing to tumor necrosis related apoptosis inducing ligand-induced synergistic apoptotic responses. Leuk Lymphoma. 2011 Jul;52(7):1290-301.
  26. Johnston JB. Mechanism of action of pentostatin and cladribine in hairy cell leukemia. Leuk Lymphoma. 2011 Jun;52 Suppl 2:43-5.
  27. Ishdorj G, Johnston JB, Gibson SB. Inhibition of constitutive activation of STAT3 by curcurbitacin-I (JSI-124) sensitized human B-leukemia cells to apoptosis. Mol Cancer Ther. 2010 Dec;9(12):3302-14.
Book Chapters
  1. Johnston JB, Seftel M. Gibson SB, Chronic Lymphocytic Leukemia. In: J.P. Greer, J. Foerster, J. Lukens, F. Paraskevas, G.M. Rodgers, and B.E. Glader (eds), Wintrobe's Clinical Hematology, 12th Edition, Baltimore, MD: Williams and Wilkins, 2008.
  2. Szwajcer D, Johnston JB, Hairy Cell Leukemia. In: J.P. Greer, J. Foerster, J. Lukens, F. Paraskevas, G.M. Rodgers, and B.E. Glader (eds), Wintrobe's Clinical Hematology, 12th Edition, Baltimore, MD: Williams and Wilkins, 2008.

Awards

Invited Seminars and Presentations at Symposia and Meetings

  1. Hernandez TA, Hewitt D, Seftel M, and Johnston JB. The improved survival of women versus men in chronic lymphocytic leukemia may be partially related to IgVH mutational status. American Assoc Cancer Res., Abstract #2210, 2008.
  2. Ishdorj G, Graham, B, Hu, X, Johnston, JB, and Gibson, SB. Lysophosphatidic acid (LPA) protected cancer cells from histone deacetylase (HDAC) inhibitor-induced apoptosis through alteration regulation of histone acetylation. American Assoc Cancer Res, Abstract #2675, 2008
  3. Johnston JB. The Epidemiology of Chronic Lymphocytic Leukemia. Western Lymphoma Group Meeting. Banff, May 2008.

Funding

DNA damage repair and development of novel anti-cancer therapeutics CancerCare Manitoba Foundation Operating grant $60,000/yr 2016 - 2018 Role: Principal Investigator Co-Investigator: Sachin Katyal An Innovative Cancer Research Model: Integrated Multidisciplinary CLL Research Cluster Research Manitoba $500,000/yr 2015 - 2020 Principal Investigator: Spencer Gibson Role: Co-Investigator Development & Maintenance of the Manitoba Chronic Lymphocytic Leukemia Databases Gilead Pharmaceuticals $60,000/yr Principal Investigator 2015-2016 Lysosome-mediated cell death in chronic lymphocytic leukemia Canadian Cancer Society Research Innovation $100,000/yr 2013 - 2015 Co-Investigator Understanding the role bendamustine alone or in combination plays in treating chronic lymphocytic leukemia Lundbeck Pharmaceuticals $50,000/yr 2014 - 2017 Principal Investigator

Professional Services

  1. Assistant Head (Clinical), Manitoba Institute of Cell Biology
  2. Clinical Director, Manitoba CLL Tumour Bank
  3. Cancer Biology Graduate Course Coordinator (36.720) (with Dr. Michael Mowat)
  4. Molecular Biology Course Coordinator for Clinical Hematology/Oncology residents
  5. Chairman for the Planning Committee for the annual Canadian CLL Meeting
  6. Member of the Planning Committee for the annual Canadian Lymphoma Meeting
  7. Coordinator for Hematology/Oncology Section Rounds
  8. Chairman of the LG Israels Annual Memorial Lecture Committee
  9. Manuscript reviewer for Blood, Cancer, Leukemia Lymphoma and Leukemia Research
  10. Scientific reviewer for Alberta Cancer Board


RIOH gratefully acknowledges the generous support of


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