
Bjørn Tore GjertsenUniversity of Bergen | UiB · Department of Clinical Science
Bjørn Tore Gjertsen
M.D., Ph.D.
About
510
Publications
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Introduction
Development of single cell phosphoprotein analysis in myeloid leukemia patient for phenotype analysis of mutations in signalling pathways, explore phosphoprotein signaling response for prognostic information in cancer, as biomarkers for therapy guidance in clinical trials and in elucidation of key physiological responses. In collaboration with Dr. McCormack, establishment of animal models and advanced molecular imaging of myelogen leukemia for development of p53- and signalling-targeted therapy.
Additional affiliations
August 1997 - August 1999
October 2010 - present
September 2007 - present
Publications
Publications (510)
Resazurin, a phenoxazine used in cell viability assays, acts in vitro as an anti‐leukaemic compound through the production of cellular reactive oxygen species (ROS) resulting in mitochondrial dysfunction and cell death. However, the in vivo tolerance and efficacy of resazurin in cancer are unknown. In this study, we investigated the in vitro and in...
The development of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, dasatinib, and bosutinib has resulted in substantial improvement of clinical outcomes in the treatment of chronic myeloid leukemia (CML). However, TKI treatment needs to be given life-long, with less than 40% of patients being able to discontinue TKI treatment and rea...
Background. Maintaining remissions in AML patients after intensive induction therapy continues to be a challenge, specifically in patients with measurable residual disease (MRD+). Immunotherapy could be an effective way to induce durable disease control for patients in complete remission. This Phase 2 trial used vididencel, an allogenic leukemia-de...
Vididencel is an active immunotherapy comprising irradiated leukemic-derived dendritic cells from the DCOne cell line, which are administered via intradermal injection. In clinical studies, vididencel treatment has been shown to be safe and feasible in treatment of patients with acute myeloid leukemia (AML), with side effects limited to local injec...
Measurable residual disease (MRD) is detected in approximately a quarter of AML chemotherapy responders, serving as a predictor for relapse and shorter survival. Immunological control of residual disease is suggested to prevent relapse, but the mechanisms involved are not fully understood. We present a peripheral blood single cell immune profiling...
e13529
Background: Access to new cancer drugs requires knowledge of biomarkers. As a consequence, there is an increasing access gap to new treatments between different cancer subgroups. Several precision medicine trials aim to address this gap through drug repurposing (1-3). IMPRESS-Norway is a national precision cancer medicine trial providing tre...
Mass cytometry by time-of-flight (CyTOF) is an emerging technology allowing for in-depth characterization of cellular heterogeneity in cancer and other diseases. Unfortunately, high-dimensional analyses of CyTOF data remain quite demanding. Here, we deploy a bioinformatics framework that tackles two fundamental problems in CyTOF analyses namely (1)...
Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the peripheral blood. Nearly half of the AML patients relapse after standard induction therapy, and new forms of therapy are urgently needed. Chimeric antigen receptor (CAR) T therapy has so far not been successful in AML due to lack o...
Monosomy 7 and del(7q) (-7/-7q) are frequent chromosomal abnormalities detected in up to 10% of patients with acute myeloid leukemia (AML). Despite unfavorable treatment outcomes, no approved targeted therapies exist for patients with -7/-7q. Therefore, we aimed to identify novel vulnerabilities. Through an analysis of data from ex vivo drug screen...
Background
Right-sided colon cancer (RCC) differs in mutation profile and risk of recurrence compared to distal colon cancer. Circulating tumour DNA (ctDNA) present after surgery can identify patients with residual disease after curative surgery and predict risk of early recurrence.
Methods
This is a prospective observational biomarker trial with...
Background. Vididencel is an allogeneic leukemia-derived dendritic cell vaccine being developed as maintenance treatment in AML patients. Intradermal vaccination using vididencel is known to induce a local skin reaction, with local antigen processing by skin dendritic cells and direct presentation to T cells as well as dendritic cells, crawling out...
Background: The standard of care (SOC) in newly-diagnosed (ND) AML patients (pts) unfit for intensive chemotherapy (IC) yields median overall survival (mOS) of 14.7 months. However, beyond 1 st line (1L), pts have limited treatment options and dismal mOS of 2.3 months (4.7 months in pre-venetoclax era), highlighting the need for more effective trea...
Diagnosis of myelodysplastic syndromes (MDS) and accurate risk assessment to tailor treatment remains challenging. High-risk MDS (hrMDS) patients who are fit enough may benefit from intensive chemotherapy followed by post-remission consolidation. The HOVON-SAKK (HO) acute myeloid leukemia (AML) trials, designed to test novel drug combinations with...
Background. Maintaining remission in AML after intensive chemotherapy continues to be a challenge, specifically in patients with measurable residual disease (MRD+). Immunotherapy could be an effective way to induce durable disease control for patients in remission. This phase 2 study used an allogenic leukemia-derived dendritic cell vaccine to indu...
Background. Active immunotherapy relies on the patient's immune system for induction of an effective immune response. Not only the frequency, number and exhaustion or activation status of CD8 T cells is important for an efficacious tumor cell lysis, but the quality, number and distribution of different antigen presenting cells is of equal importanc...
Introduction: The combination therapy of Venetoclax (Ven) and Azacitidine (Aza) has shown remarkable improvements in the treatment of acute myeloid leukemia (AML) patients not eligible for chemotherapy. Nevertheless, patients with TP53-mutated AML are more prone to have a refractory disease or develop rapid resistance. A recent study indicated that...
Acute myeloid leukemia can be treated by intensive chemotherapy. However, this treatment is unsuitable for a subset of patients because of age and/or co-morbidities. Such patients benefit from hypomethylating agents and venetoclax but frequently develop resistance to this treatment regimen. This calls for the development of novel drugs that can pro...
Clinical decision-making based on measurable residual disease (MRD) in acute myeloid leukemia (AML) is steadily increasing; therefore, accurate MRD results are imperative. Multi-parameter flow cytometry (MFC) is often used due to wide availability, particularly when no suitable mutation is present. Two approaches are most common in MFC-MRD: 1. Leuk...
Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment...
Intensive induction chemotherapy achieves complete remissions (CR) in >60% of patients with acute myeloid leukemia (AML) but overall survival (OS) is poor for relapsing patients not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be...
Background: In this trial, mCRPC patients were treated with DC-based CryoIT as monotherapy or combined with checkpoint inhibitors, enabling systemic attacks on heterogenous cancer cells by lymphocytes introduced to tumor-associated antigens.Primary endpoints showed that the treatment was safe. The secondary aims included survival and biologic outco...
e14708
Background: Despite improvements, metastatic castration-resistant prostate cancer (mCRPC) still has dismal overall survival (OS). We treated 18 mCRPC patients with dendritic cell (DC)-based cryoimmunotherapy (CryoIT) as monotherapy or combined with checkpoint inhibitors to determine safety and immune response. Methods: mCRPC patients were bi...
In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilot...
Monosomy 7 and del(7q) (-7/-7q) are frequent chromosomal abnormalities detected in up to 10% of acute myeloid leukemia (AML) patients. Despite unfavorable treatment outcomes, no approved targeted therapies exist for patients with -7/-7q. Therefore, we aimed to identify novel therapeutic vulnerabilities in AML with -7/-7q. Through an analysis of dat...
Li-Fraumeni syndrome (LFS) is a cancer predisposing syndrome
caused by pathogenic germline TP53 gene mutations with important therapeutic and prognostic implications for many types of cancer. A small proportion of LFS patients develop B-cell lymphoblastic leukemia (B-ALL) in adult years. Standard treatment often proves inadequate, but immunotherapy...
Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations cou...
Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machin...
NPM1-mutated AML represents a WHO leukemia entity with unique pathological and clinical features. Little is known about the characteristics of "therapy-related" NPM1-mutated AML. We compared the genetics, transcriptional profile and clinical outcome of therapy-related NPM1-mutated AML (t-NPM1 AML), de-novo NPM1-mutated AML (dn-NPM1 AML) and therapy...
Cellular therapies for burn wound healing, including the administration of mesenchymal stem or stromal cells (MSCs), have shown promising results. This review aims to provide an overview of the current administration methods in preclinical and clinical studies of bone-marrow-, adipose-tissue-, and umbilical-cord-derived MSCs for treating burn wound...
Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermed...
The use of single-cell profiling of phenotypes is suggested to inform about chemoresistance and lack of treatment response in cancer. Mass cytometry by time-of-flight (CyTOF) allows high throughput multiparametric analysis at the single-cell level to perform for in-depth characterisation of heterogeneity in leukemia. However, computational identifi...
e13634
Background: Norway, a country with a publicly funded health care system, was in 2018-19 lagging behind with respect to implementation of precision cancer medicine (PCM). Methods: Our approach mid-2019 was very simple and set out three aims: i) To establish access to advanced molecular diagnostics to allow identification and stratification of...
Background
Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tiss...
Background: Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tis...
Background: A fundamental hallmark of cancer cells is their ability to sustain proliferative signaling and cell survival, reflected in a cellular chemotherapy response that is poorly understood. We questioned whether chemotherapy modulated phospho-signaling at 4 and 24 h in vivo could provide information about long-term survival in acute myeloid le...
Development of cancer therapy follows three main pathways: mutation-driven drug development, immunomodulatory therapy, and evolution of conventional chemo- and radiotherapy. All these therapeutic modalities require more precise biomarkers, not only for increasing accuracy and enhancing efficiency but also to avoid unnecessary toxicity for the patie...
Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomize...
Bone regeneration from mesenchymal stromal cells (MSC) is attributed to comprehensive immune modulation mediated by the MSC. However, the temporal and spatial regulation of these immune responses has not yet been described. The aim of the present study was to assess the local and systemic innate immune responses to implantation of biphasic calcium...
Background
Vaccine-induced immune thrombotic thrombocytopenia (VITT) has so far only been reported after adenovirus vector SARS-CoV-2 vaccines.
Objective
We report findings in a 25-year-old woman who presented with thrombocytopenia, venous thrombosis, elevated D-dimer levels, and high levels of platelet-activating antibodies to platelet factor 4 (...
We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of...
Background. Persistence of measurable residual disease (MRD) is a poor prognostic factor and predicts relapse in acute myeloid leukemia (AML). In a phase I study, the allogeneic leukemia-derived dendritic cell vaccine, DCP-001, has shown safety and humoral and cellular immune responses (A.A. van de Loosdrecht, et al. Cancer Immunol. Immunother. 201...
Background: Relapsed (REL) & refractory (REF) r/r AML pts unsuitable for intensive therapy (IT) due to age or co-morbidities, have limited treatment options. Low-dose cytarabine (LDAC) demonstrated limited survival benefit (mOS ≤6 months), highlighting the significant unmet need for new treatments in this patient population. Bemcentinib (BEM) is an...
Treatment of acute myeloid leukaemia (AML) relies on decades-old drugs, and while recent years have seen some breakthroughs, AML is still characterised by poor prognosis and survival rate. Drug repurposing can expedite the preclinical development of new therapies, and by nanocarrier encapsulation, the number of potentially viable drug candidates ca...
Objectives
Treatment‐free remission (TFR) has emerged as a treatment goal in chronic myeloid leukemia in the chronic phase (CML‐CP). Attempts to increase proportion of patients achieving TFR include combination of tyrosine kinase inhibitors (TKI) and other drugs. Interferon‐α in addition to TKI has shown promising efficacy but with dose‐dependent t...
Objectives
This study aims to retrospectively assess C‐lectin‐like molecule 1 (CLL‐1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL‐1 bimodal associations with leukemia and patient‐specific characteristics.
Methods
Flow cytometry assays were performed to assess the deeper immu...
Incidence, molecular presentation and outcome of acute myeloid leukaemia (AML) is influenced by sex, but little attention has been directed at untangling sex‐related molecular and phenotypic differences between female and male patients. While increased incidence and poor risk is generally associated with a male phenotype, the poor prognostic FLT3 i...