Myeloid leukemia occurs in two forms, the rapidly progressing acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), in which leukemic cells expand slowly in bone-marrow and other blood-forming organs. AML and CML cells are frequently sensitive to the anti-leukemic functions of natural killer (NK) cells and T cells, and therapies aiming to boost the function of these cells may be useful in eradicating the leukemic clone.
A major aim of the research in our research group (Martner Lab) is to define, utilizing a translational approach, the role of cytotoxic lymphocytes in AML and CML with focus on mechanisms of immunosuppression (oxygen radical production by leukemic cells, myeloid-derived suppressor cells) that may stifle the immune-mediated clearance of leukemic cells. The studies are, in part, based on our finding of a novel mechanism of immunosuppression in leukemia, in which myeloid leukemic cells produce reactive oxygen species (ROS) via the enzyme NOX2 that kill adjacent NK cells and T cells by inducing apoptosis.
A parallel and related aim is to define mechanisms of differentiation of myeloid leukemic cells to form the basis for treatments that promote the maturation of leukemic cells into functional leukocytes.
A close collaboration with clinical units allow the recovery of primary leukemic cells, to be used for in vitro and in vivo studies. Furthermore, several leukemic animal models, including genetic leukemia models, transplantation models, and xenograft models, are being utilized in the studies. Advanced multicolor flow cytometry and FACS-sorting are frequently utilized techniques in the lab.
Current group members
Anna Martner, PhD, Associate Professor
Roberta Kiffin, PhD
Hanna Grauers Wiktorin, PhD
Mohammad Arabpour. PhD
Belson Rugwizangoga, MD, PhD student
Malin Nilsson, PhD student
Sanchari Paul, PhD student
Andreas Törnell, PhD student
Yarong Tian, PhD student (associated)
- NOX2 inhibition reduces oxidative stress and prolongs survival in murine KRAS-induced myeloproliferative disease.
Aydin, E., A. Hallner, H. Grauers Wiktorin, A. Staffas, K. Hellstrand, A. Martner. (2019) Oncogene 38:1534-1543.
- NOX2 in autoimmunity, tumor growth and metastasis.
Martner, A., E. Aydin, K. Hellstrand. (2019) J Pathol 247:151-154.
- Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade.
Grauers Wiktorin, H., M.S. Nilsson, R. Kiffin, F.E. Sander, B. Lenox, A. Rydstrom, K. Hellstrand, A. Martner. (2019) Cancer Immunol Immunother 68:163-174.
- Isolated limb perfusion with melphalan triggers immune activation in melanoma patients.
Johansson, J., R. Kiffin, A. Andersson, P. Lindner, P.L. Naredi, R. Olofsson Bagge, A. Martner. (2018) Front Oncol 8:570.
- Anti-Leukemic properties of histamine in monocytic leukemia: The role of NOX2.
Kiffin, R., H. Grauers Wiktorin, M.S. Nilsson, J. Aurelius, E. Aydin, B. Lenox, J.A. Nilsson, A. Stahlberg, F.B. Thoren, K. Hellstrand, A. Martner. (2018) Front Oncol 8:218.
- Role of NOX2 for leukaemic expansion in a murine model of BCR-ABL1(+) leukaemia.
Grauers Wiktorin, H., T. Nilsson, E. Aydin, K. Hellstrand, L. Palmqvist, A. Martner. (2018) Br J Haematol 182:290-294.
- Role of NOX2-derived reactive oxygen species in NK cell-mediated control of murine melanoma metastasis.
Aydin, E., J. Johansson, F.H. Nazir, K. Hellstrand, A. Martner. (2017) Cancer Immunol Res 5: 804-11.
- Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.
R. Kiffin, A. Stahlberg, M. Brune, R. Foà, K. Hellstrand, F. B. Thoren, A. Martner. (2017) Cancer Immunol Immunother 66: 1473-84.
- Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia.
Rydstrom, A., A. Hallner, J. Aurelius, F.E. Sander, E. Bernson, R. Kiffin, F.B. Thoren, K. Hellstrand, and A. Martner. (2017) J Leukoc Biol 102: 467-74.
- Role of natural killer cell subsets and natural cytotoxicity receptors for the outcome of immunotherapy in acute myeloid leukemia.
Martner, A., A. Rydström, R.E. Riise, J. Aurelius, H. Anderson, M. Brune, R. Foa, K. Hellstrand, F.B. Thoren. (2016) Oncoimmunology 5: e1041701.
More group Anna Martner publications on PubMed