Bjørn Tore Gjertsen
The Signaling-Targeted Research Group.
About the research group
Bjørn Tore Gjertsen, MD (1992), PhD (1995), is professor of hematology (2007-) at the University of Bergen (UiB), and senior consultant hematologist (2007-) at Haukeland University Hospital. Gjertsen was a postdoc at the MD Anderson Cancer Center, Houston, from 1997–1999, a part-time postdoc at the UiB from 2001–2005 and completed his specialist training in clinical hematology in 2007. From 2016–2022, he served as co-director for CCBIO. From 2010 to 2018, Gjertsen developed a phase I clinical trials unit at Haukeland University Hospital. His clinical practice in hematology is focused on clinical trials in chronic and acute myeloid leukemia (AML). His laboratory is working on intracellular signal transduction and the regulation of the tumor suppressor protein p53. He has a special interest in single-cell analysis and detection of circulating tumor cells for early response evaluation.
Dr. Gjertsen is a founding member and chair of the Norwegian AML Group and the Nordic AML Group, and is a member of EHA, ASH, ASCO, and the Nordic CML Study Group. He is the co-founder of four small biotech companies.
Brief group presentation and history
The group was built on Gjertsen’s experiences during his PhD fellowship (kinases and phosphatases in regulation of cell death) and his two postdoc periods (MDACC, Houston, on p53 and Bcl-2). The second postdoc in Bergen was used to establish models of acute myeloid leukemia, in vitro and in vivo, and at this time, the power of primary cells from cancer patients was made clear. Three publications formed the way forward: Gausdal et al. on early proteome modulation after the start of chemotherapy, including regulation of phosphorylation. Then the single-cell phospho-flow paper describing that functional assays on living tumor cells could indicate prognosis. This was conceptually copied in CML patients dosed with a specific kinase inhibitor, indicating that response to therapy can be identified after hours and days, not weeks and months. With support from the Norwegian Cancer Society and a repatriation grant in functional genomics from the Research Council of Norway, a research laboratory was established.
Research focus
The Gjertsen group focuses on single-cell immune and signaling profiling in early response evaluation of AML and CML patients, as well as therapy development in AML using single-cell analysis as companion diagnostics.
Subprojects
KG Jebsen Centre for Myeloid Blood Cancer:
This opened in September 2024 and acts as an overarching structure to support the establishment of new single-cell technologies, validation of these technologies, including mass cytometry, and outreach to secure larger biobank materials from clinical trials.
Repurposing drugs in cancer:
Focusing on AML and with preliminary data indicating clinical benefit, the concept will be tested in advanced cancer with particularly low survival. Companion diagnostics through single-cell profiling should improve the precision of the therapy chosen. Results indicate that the ERK1/2 pathway and p53 protein modulation, as well as the mutational status of TP53 and signaling, are candidate companion diagnostics.
Single-cell immune and signaling profiling in cancer:
This project aims to show the potential of single-cell immune and signaling profiling in cancer prognostication and response evaluation, based on biobanked peripheral blood in small clinical trials. Immune profiling with intracellular signaling demonstrates that AML patients in complete remission are very different from healthy individuals. Imaging mass cytometry can be used in skin biopsies to examine the mechanisms involved in cell vaccination with dendritic cells. Advanced cancer patients can be response evaluated by peripheral blood single cell profiling.
Tumor suppressor p53 protein profiling in cancer:
Profiling of p53 isoforms and posttranslational modifications in single cells will be developed and connected to the signaling state and phenotype of the cell.
Translational, clinical, and societal importance
The group has developed an advanced biomarker program for clinical studies. Gjertsen developed a phase I trials unit at HUS, and the impact of CCBIO Seminars and the yearly Symposium led to more phase I clinical trials in Bergen. CCBIO contributed strongly to introducing immunotherapy in cancer, particularly the introduction of immune checkpoint blockers through clinical trials at the trial unit. Materials for advanced biomarker analysis are still being collected and analyzed, and in the coming years, several publications are planned towards liquid biopsy.
Future perspectives from 2024
The CCBIO biomarker concept and the focus on tumor-host interactions have made visible limitations in infrastructure and spawned two small biotech startups: Alden Cancer Therapy and Há Biotechnology. The last biotech, Bjørgvin Technology Group, aims to bring the compassionate diagnostics test in single cell format into effective low toxic therapy to keep aggressive cancer in check.
Upcoming scientific publications will include work on circulating tumor cell determination in peripheral blood combined with single-cell immune- and signaling profiling. Single cell profiling will be examined for response evaluation in advanced cancer patients treated with immunological checkpoint blockers as well as in patients surgically treated for colorectal cancer. The immune profile aspect will be used in understanding the most intense and complicated treatment of allogeneic hematopoietic stem cell transplantation. In this interphase together with cryoimmunotherapy, the biomarker aspect of engineered T cells will be established and developed.
Results from the CoE period 2013-2024
Most important results
In general, single cell profiling of peripheral blood leukocytes seems to include information about the prognosis and predict the therapeutic effect of cancer therapy. By monitoring intracellular signaling pathways, transcription factors and cell death regulators, response is possible to determine after hours and days. If the patient is a non-responder, therapy can be adapted or replaced weeks or months before the current standard of care.
Most important papers
- Tislevoll BS et al. Early response evaluation by single cell signaling profiling in acute myeloid leukemia. Nature Communications, 2023. PMID: 36611026.
- Gullaksen SE et al. Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukaemia treated with nilotinib. Haematologica 2017. PMID: 28522574.
- Hellesøy M et al. Sex disparity in acute myeloid leukaemia with FLT3 internal tandem duplication mutations: implications for prognosis. Mol Oncol. 2021. PMID: 34101344.
- McCormack E et al. Multiplexed monoclonal antibodies: A new strategy in preclinical time domain imaging of acute myeloid leukemia. Blood. 2013. PMID: 23243270.
- Omsland M et al. Tyrosine kinase inhibitors and interferon-α increase tunneling nanotube (TNT) formation and cell adhesion in chronic myeloid leukemia (CML) cell lines. FASEB J. 2020. PMID: 31945226.
- Sulen A et al. Elevated monocyte phosphorylated p38 in nearby employees after a chemical explosion. Sci Rep. 2016. PMID: 27380711.
- Andresen V et al. Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia. Cell Death Dis. 2016. PMID: 27906185.
CCBIO significance
"The single most important element in the center has been the passionate and deeply involved Scientific Advisory Board, combined with a Centre Director with patience and well-structured leadership. Multiple collaborations have been created, and likely the question of success or societal benefit will not be answered in 5 to 10 years. Within the interest of CCBIO, we have been able to establish a collaboration in immunotherapy and introduced unique cell therapy through the concept of cryoimmunotherapy."