Group Anna Martner

Research summary

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.

Research tools and resources

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
Jesper Waldenström, PhD, Postdoc
Andreas Törnell, PhD student
Malin Nilsson, PhD student
Mustafa Kaya, PhD student
Nuttida Issdisai, PhD student
Olivia Johnsson, PhD student
Sanchari Paul, PhD student
Jean Bosco Munyemana, PhD student (associated)

Selected publications

1. Transient and durable T cell reactivity after COVID-19.
   Martner A, Grauers Wiktorin H, Törnell A, Ringlander J, Arabpour M, Lindh M, Lagging M, Nilsson S, Hellstrand K. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203659119. doi: 10.1073/pnas.2203659119. Epub 2022 Jul 12.PMID: 35858456 
    

2. Impact of CYBA genotypes on severity and progression of multiple sclerosis.
   Törnell A, Kiffin R, Haghighi S, Mossberg N, Andersen O, Hellstrand K, Martner A. Eur J Neurol. 2022 May;29(5):1457-1464. doi: 10.1111/ene.15259. Epub 2022 Feb 6.PMID: 35073438
    

3. Rapid cytokine release assays for analysis of SARS-CoV-2-specific T cells in whole blood.
   Törnell A, Grauers Wiktorin H, Ringlander J, Arabpour M, Nilsson MR, Nilsson S, Kiffin R, Lindh M, Lagging M, Hellstrand K, Martner A. J Infect Dis. 2022 Jan 12:jiac005. doi: 10.1093/infdis/jiac005. Online ahead of print.PMID: 35022764
    

4. Direct and Indirect Regulators of Epithelial-Mesenchymal Transition-Mediated Immunosuppression in Breast Carcinomas.
   Dongre A, Rashidian M, Eaton EN, Reinhardt F, Thiru P, Zagorulya M, Nepal S, Banaz T, Martner A, Spranger S, Weinberg RA. Cancer Discov. 2021 May;11(5):1286-1305. doi: 10.1158/2159-8290.CD-20-0603. Epub 2020 Dec 16.PMID: 33328216 
    

5. 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.
    
6. 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.
    
7. 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.
    
8. 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.
    
9. 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.
    
10. Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis.
    Aurelius J, Thorén FB, Akhiani AA, Brune M, Palmqvist L, Hansson M, Hellstrand K, Martner A. Blood. 2012 Jun 14;119(24):5832-7. doi: 10.1182/blood-2011-11-391722. Epub 2012 May 1.PMID: 22550344 

More group Anna Martner publications on PubMed