Results from Research

FHRB Biobank Research

 

2023

Study Title: Developing a Precision Medicine Strategy to Diagnose and Treat Refractory Acute Myeloid Leukemia

Principal Investigator: William Stanford, Ottawa Hospital Research Institute, Canada

AML is treated with conventional induction therapy. However, some patients do not respond to treatment due to a dysregulation of the MTF2/PRC2 gene regulatory network (GRN). Some factors in this GRN can potentially be used as biomarkers to diagnose and guide treatment options for AML patients refractory to standard induction chemotherapy (rAML). The objective is to develop a clinical biomarker assay to diagnose rAML. Newly developed flow cytometry assay to quantitate H3K27me3 and MTF2 expression in diagnostic AML bone marrow samples will be validated to determine significant correlation between biomarker expression and patient response to standard induction chemotherapy. Also, biomarker expression in diagnostic AML bone marrow samples from a phase 1b clinical trial investigating the safety and efficacy of a MDM2 inhibitor in combination with induction drugs to treat AML will be analyzed. This study will determine whether rAML patients, as predicted by the biomarkers, will benefit from this novel treatment regimen.

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Study Title: Development of new analysis methods to improve treatment and better detect disease relapse in patients with AML and MDS

Principal Investigator: Anna Robelius, Uppsala University, Sweden

The scientific aim of the project is to examine longitudinal blood and bone marrow samples from patients with myeloid malignancies in the blood and to study the extent to which peripheral blood tests can replace and/or complement today's conventional bone marrow tests using a new and significantly more sensitive analysis method.

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Study Title: Innovative approaches to combat aggressive acute myeloid leukemia

Principal Investigator: Mika Kontro, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The study will investigate the response of cancer cells to novel programmed cell death, or apoptosis, based therapies in AML subtypes that are difficult to treat. One such subtype is TP53-mutated AML, in which no good treatment options are currently available. The aim of this study is to unravel the molecular mechanisms behind TP53 mutation-mediated venetoclax resistance in myeloid malignancies (AML/MDS). Simultaneously it seeks to identify novel strategies to effectively target this challenging subset of patients. Since the TP53 mutation is the most common mutation in cancer, the project may have far-reaching implications for the treatment of other cancers.

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2022

Study Title: A pan-cancer approach connecting tumor molecular profiles and individual
health information for discoveries and new precision cancer medicine solutions (iCAN)

Principal Investigator: Tomi Mäkelä, University of Helsinki

The iCAN biobank study aims to establish a resource enabling dynamic linking of tumor molecular profiling with rich phenotypic endpoints of the patient for discoveries and contributing to improving precision cancer medicine. To this end iCAN aims to combining genomic, transcriptomic, and immunooncologic profiling of up to 15 000 cases of haematological and solid tumours with associated health data of the patient increases understanding of the complex interactions resulting in actionable insights and development of cutting-edge technologies. Providing benefits for cancer patients by iCAN project is accomplished firstly through the acceleration of scientific discovery in cancer care, diagnostics, and treatment, and secondly through systematic, proactive interaction with the cancer patient and carer community. The ultimate goal in the project is based on broader democratic principles of citizenship, accountability and transparency.

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Study Title: Characterization of cancer cells and immune cells in bone marrow and blood, their interaction and significance for disease development

Principal Investigator: Kristine Misund, Norwegian University of Science and Technology, Norway

The objective is to study whether long-term survivors have a more efficient anti-tumor immune response than patients with poor prognosis. Myeloma is a heterogeneous cancer disease that resides within a complex microenvironment in the bone marrow. Although the average survival of myeloma patients is 5-6 years, there is a large variation of overall survival, from months in the very aggressive high-risk tumors, to decades for less aggressive and slow growing tumors. In this project tumor-immune interactions are investigated between patients surviving for many years versus those with a short aggressive disease course with modern technologies (CyTOF analysis, scRNAseq and TCR sequencing). Better understanding of the anti-tumor immune response will enable to modify this activity for a therapeutic benefit.

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2021 

Study Title: aCOX-2 autoantibody in hematological disorders

Principal Investigator: Satu Mustjoki, Hematology Research Unit Helsinki, University of Helsinki

Our goal is to understand the frequency and the clinical importance of anti-COX-2 autoantibodies (aCOX-2 Ab) in hematological disorders. Analysis of a large cohort will help to define the specificity of the aCOX-2 Ab in aplastic anemia (AA) and to characterize its applicability as a differential diagnostic tool in bone marrow failure diseases. In the next steps, we further widen the scope to assess the applicability of the marker in differentiating AA from other hematological disorders. We also aim to study whether aCOX-2 Ab has a role in AA pathogenesis.

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Study Title: The use of optical genome mapping as a generic cytogenetic test in CLL and MDS

Principal Investigator: Tuomo Mantere, University of Oulu

The aim of this study is to assess whether the novel optimal genome mapping (OGM) technology could serve as a single generic cytogenetic test and identify all the chromosomal aberrations that have previously been identified by classical cytogenetic approaches from patients with CLL or MDS. In addition, the aim is to investigate whether any cryptic or novel structural variants (SVs) of potential clinical relevance can be identified with this new approach.

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Study Title: Drug sensitivity and genomic analyses of Mature T-cell lymphomas/leukemias

Principal Investigator: Satu Mustjoki, Hematology Research Unit, University of Helsinki

The aim of the study is to improve the efficacy and safety of T-PLL and T-LGLL leukemia treatments. The study will test established cancer drugs and also novel STAT inhibitors on primary MaTCL cells ex vivo.

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Study Title: Epidemiological survey of immunotherapy targets in myeloid malignancies

Principal Investigator: Markus Vähä-Koskela, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The aim of the study is to understand progression of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) at single cell level, and to profile patient samples for eligibility for novel immunotherapies.

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Study Title: Research Project FinnGen: Combining genetic and electronic health record data to improve drug discovery

Principal Investigator: Aarno Palotie, University of Helsinki

FinnGen study is research project with both public and private sector involvement. The main aim of the FinnGen study is to combine 500 000 Finnish study participants’ genomic data and health data in order to improve understanding of genetic mechanisms behind diseases and development of new potential drug targets.

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2020

Study Title: Acute Myeloid Leukemia Leukemic Initiating Cells: contribution of hypoxia/HIF pathway to chemoresistance and relapse

Principal Investigator: Talia Velasco Hernandez, Josep Carreras Leukaemia Research Institute, Spain

The objective of this study is to analyze the transcriptome by single cell RNA sequencing of the leukemic initiating cells of AML samples of various specific cytogenetic groups.

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Study Title: DNA methylation as a biomarker and therapeutic target in T-cell Acute Lymphoblastic Leukemia

Principal Investigator: Riikka Lund and Riina Kaukonen, University of Turku

The aim of this study is to characterize the clonal DNA methylation and the corresponding RNA expression with respect to the drug resistant/responsive phenotypes of individual pediatric, younger adults (19-40 year) and in adults (>40 year) T-ALL patient cells in order to identify DNA methylation biomarkers that could predict therapy outcome.

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Study Title: Investigation of the microRNA controlled dysfunctional T cell compartment in the stem cell niche of Myelodysplastic syndrome patients

Principal Investigator: Dagmar Quandt, Institute for Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Germany

The objective of this study is to identify differential expressed cell type specific (T cells, progenitor stem cell) microRNA profiles in low-risk and high-risk MDS patients and non-MDS controls and to discover the contribution of the dysregulated T cell compartment to disease onset and progression. The final aim is to propose new therapeutic avenues related to microRNAs and/or T cells for the control of progression from low-risk to high-risk MDS.

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Study Title: Immune surveillance and lenalidomide discontinuation in patients with del5q MDS

Principal Investigator: Mikko Myllymäki, Hematology Research Unit Helsinki, University of Helsinki

The objective of this study is to analyze immunophenotypes of del5q myelodysplastic syndrome samples (MSDs) and determine their responses to lenalidomide treatment.

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Study Title: Molecular fingerprints for bone marrow cells, MORE

Principal Investigator: Merja Heinäniemi, Institute of Biomedicine, University of Eastern Finland

The overall goal of this study is to harness the full molecular fingerprint of bone marrow cells for accurate identification of clinically relevant cell states.

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Study Title: Role of Clever-1 on acute myeloid leukemia (AML)

Principal Investigator: Sirpa Jalkanen, MediCity, University of Turku

The objective of this study is to analyze the effects of immunotherapy Clevegen on AML cell function and viability by utilizing bone marrow collected from AML patients.

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2019

Study Title: To identify the AML blast population responsible for relapse in FLT3-ITD+/NPM1- AML patients using single cell RNA seq

Principal Investigator: Eva Szegezdi, National University of Ireland, Ireland

The objective of this study is to identify the cell populations participating in the development of relapses in acute myeloid leukemia.

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Study Title: Early detection of relapsed AML in children

Principal Investigator: Henrik Hasle, Aarhus University Hospital Skejby, Denmark

The objective of this study is to determine the possibility of follow-up of acute myeloid leukemia in children using patient-specific genetic markers.

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Study Title: Drug sensitivity testing and molecular profiling of plasma cell dyscrasias to identify novel treatments and the indicators of response

Principal Investigator: Caroline Heckman, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The objective of this study is to identify new pharmaceutical agents to treat multiple myeloma, plasma cell leukemia and amyloidosis.

Published articles: 

Miettinen et al 2021: Aminopeptidase Expression in Multiple Myeloma Associates with Disease Progression and Sensitivity to Melflufen. Cancers 13 (7); 1527. https://doi.org/10.3390/cancers13071527

Liu, Minxia el al 2021: S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma. Frontiers in Cell and Developmental Biology 9. https://doi.org/10.3389/fcell.2021.723016

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Study Title: The determinants of drug response in acute lymphoblastic leukemia

Principal Investigator: Caroline Heckman, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The objective of this study is to improve the treatment of acute lymphoblastic leukemia in children and young adults.

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2018

Study Title: Genome-wide association study of acute myeloid leukaemia (AML)

Principal Investigator: James Allan, Northern Institute for Cancer Research, Newcastle University, UK

The objective of this study is to identify new alleles associated with acute myeloid leukemia.

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Study Title: Improving outcome for patients with Poor Risk Acute Myeloid Leukaemia

Principal Investigator: Jude Fitzgibbon, Barts Cancer Institute, Queen Mary University of London, UK

The objective of this study is to enhance our understanding of the multiple genetic and biochemical factors underlying acute myeloid leukemia with a poor prognosis. The objective is to identify new targets for pharmaceutical agents and markers to identify patients likely to benefit from these drugs.

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Study Title: Comprehensive profiling of chronic (CMML) and juvenile (JMML) myelomonocytic leukemia aiming to identify novel targets for treatment

Principal Investigator: Satu Mustjoki, Hematology Research Unit Helsinki, University of Helsinki

The objective of this study is to identify novel methods to treat chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia.

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Study Title: Activity of the peptidase enhanced alkylating agent melflufen in light chain amyloidosis and indicators of response

Principal Investigator: Caroline Heckman, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The objective of this study is to enhance our understanding of the molecular genetic background of light chain amyloidosis and to examine the usability of melflufen in the treatment of this disease.

Published articles:

Flanagan et al 2022: The Peptide–Drug Conjugate Melflufen Modulates the Unfolded Protein Response of Multiple Myeloma and Amyloidogenic Plasma Cells and Induces Cell Death. HemaSphere 6 (3). https://doi.org/10.1097/HS9.0000000000000687

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2017

Study Title: Assessment of plasma cell content and viability of biobanked multiple myeloma bone marrow samples

Principal Investigator: Caroline Heckman, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The objective of this study is to assess the quality of bone marrow samples collected from patients with multiple myeloma and stored in a biobank.

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Study Title: Integrated platform of novel glycomic and proteomic approaches to investigate structural and functional changes of blood malignancies including: Multiple Myeloma (MM), Acute Myeloid Leukemia (AML) and Amyloidosis.

Principal Investigator: Peter O'Gorman, Mater Misericordiae University Hospital, Ireland

The objective of this study is to determine the progress of leukemias and their response to therapies using glycomic and proteomic approaches for multiple myeloma, acute myeloid leukemia and amyloidosis.

Published articles: 

Dowling et al 2021: Identification of Protein Biomarker Signatures for Acute Myeloid Leukemia (AML) Using Both Nontargeted and Targeted Approaches. Proteomes 9 (4); 42. https://doi.org/10.3390/proteomes9040042

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Study Title: Next generation leukemia diagnostics and therapy through p53 isoforms analysis

Principal Investigator: Bjørn Tore Gjertsen, University of Bergen, Norway

The objective of this study is to determine the prevalence of p53 isoforms in primary acute myeloid leukemia, and to assess whether they could be used as diagnostic markers during the course of treatment planning.

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2016

Study Title: Clonal lymphopoiesis in the pathogenesis of bone marrow failure syndromes

Principal Investigator: Satu Mustjoki, Hematology Research Unit Helsinki, University of Helsinki

The objective of this study is to map somatic mutations presenting in the lymphatic cells of patients with aplastic anemia or myelodysplastic syndrome (MDS). The detected mutations are characterized and their functional effects determined. One additional aim is to identify new targets for pharmaceutical agents.

Published articles: 

Lundgren et al 2021: Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia. Leukemia 35; 1365-1379. https://doi.org/10.1038/s41375-021-01231-3.

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Study Title: Towards curative therapy of Philadelphia chromosome-positive acute lymphoblastic leukemia

Principal Investigator: Satu Mustjoki, Hematology Research Unit Helsinki, University of Helsinki

The objective of this study is to identify novel alternatives for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. An additional objective is to determine the molecular and cell-specific markers predicting good response to tyrosine kinase inhibitors to identify the patients who do not need a stem cell transplant as early as possible.

Published articles:

Hohtari et al 2022: Copy number alterations define outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica 107(8):1971-1976. https://doi.org/10.3324/haematol.2021.280578

Hohtari et al 2022: Targeting Apoptosis Pathways With BCL2 and MDM2 Inhibitors in Adult B-cell Acute Lymphoblastic Leukemia. Hemasphere 6 (3). https://doi:10.1097/HS9.0000000000000701

Hohtari et al 2019: Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL. Leukemia 33; 1570-1582. https://doi.org/10.1038/s41375-018-0360-1

Dufva et al 2019: Integrated drug profiling and CRISPR screening identify essential pathways for CAR T cell cytotoxicity. Blood 135 (9); 597-609. https://doi.org/10.1182/blood.2019002121

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Study Title: Molecular Genetics and Biology of Myeloproliferative Neoplasms

Principal Investigator: Outi Kilpivaara, Genome-scale biology (GSB) research program, University of Helsinki

The objective of this study is to determine how genetic factors contribute to the development and clinical picture of myeloproliferative diseases (e.g. polycythemia vera, essential thrombocytosis and myelofibrosis). The objective is to improve the diagnostics and treatment of these diseases.

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Study Title: Molecular Genetics and Biology of Myeloproliferative Neoplasms

Principal Investigator: Outi Kilpivaara, Genome-scale biology (GSB) research program, University of Helsinki

The objective of this study is to determine how genetic factors contribute to the development and clinical picture of myelodysplastic syndrome and acute myeloid leukemia. The focus of the study is on inherited genetic factors, in particular.

Published articles:

Wartiovaara-Kautto et al 2018: Germline alterations in a consecutive series of acute myeloid leukemia. Leukemia 32;2282-2285. https://doi.org/10.1038/s41375-018-0049-5

Douglas et al 2019: ERCC6L2 defines a novel entity within inherited acute myeloid leukemia. Blood 133 (25); 2724-2728. https://doi.org/10.1182/blood-2019-01-896233

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Study Title: Assessment of the possibilities of molecular medicine in sensitive diagnostics and personalized therapy response evaluation in myelodysplastic syndromes and related myeloid malignancies (MDS-MOLE-2015)

Principal Investigator: Freja Ebeling, Hematology Outpatient Clinic, Helsinki University Hospital (HUS)

The objective of this study is to improve current diagnostics and treatment of myelodysplastic syndrome by studying genetic markers.

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Study Title: A systems medicine study to identify novel therapies for blood cancer patients

Principal Investigator: Caroline Heckman, Institute for Molecular Medicine Finland (FIMM), University of Helsinki

The objective of this study is to identify new forms of treatment and response indicators to measure the effects of therapies in leukemias by using drug-sensitivity profiling and exome and RNA sequencing, for example.

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2015

Study Title: Personalized Systems Medicine Strategy for Acute Myeloid Leukemia

Principal Investigator: Olli Kallioniemi, Science for Life Laboratory, Karolinska Institutet, Sweden

The objective of this study is to determine how leukemia cells respond to several hundreds of pharmaceuticals in vitro. The leukemia cells are collected from patients with acute myeloid leukemia. The results are then combined with the genetic, transcriptomic and proteomic profiles of the cells. The objective is to improve our understanding of the factors participating in successful response to therapy.

Published articles: 

Ianevski et al 2021: Patient-tailored design for selective co-inhibition of leukemic cell subpopulations. Science advances 7 (8). https://doi.org/10.1126/sciadv.abe4038

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Study Title: Novel molecular markers for disease activity of acute myeloid leukemia

Principal Investigator: Jukka Westermarck, Turku Centre for Biotechnology, University of Turku and Åbo Akademi

The objective of this study is to identify new markers that might predict the response to therapy in patients with acute myeloid leukemia already at the time of diagnosis. The study group is interested in genetic markers, in particular.

Published articles:

Mäkelä et al 2021: Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias. Clin Cancer Res 27 (10); 2848-2860. https://doi.org/10.1158/1078-0432.CCR-20-3679

Mäkelä et al 2019: Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia. Cancers 11; 1774. https://doi.org/10.3390/cancers11111774