Myelodysplastic syndromes – Eva Hellström Lindberg group

My research program aims at understanding disease mechanisms in MDS and to improve outcome of MDS patients and is closely linked to the MDS Clinic at the Department of Hematology, Karolinska University Hospital. The MDS research group consists of clinical scientists, cell and molecular biologists, technicians and a research nurse who together address clinically relevant scientific problems. Research students encompass both junior hematologists and young preclinical scientists.

Photo of Eva Hellström Lindberg research group

About our research

Mission of the research group 

The long-term goal is to improve cure rates and symptom-free survival for patients with myelodysplastic syndromes (MDS) through unfolding novel disease mechanisms and exploring innovative therapeutic approaches. We aim to gain synergy between a large successful MDS and bone marrow failure clinical practice, comprehensive biobanking and registries, and experimental cellular and molecular research. During the forthcoming period, we will further develop the KI MDS Biobank consisting of >1500 consecutive patients, many with repeated bone marrow sampling, a majority with targeted DNA sequencing and complete transfusion history, and a large proportion with full-length RNA sequencing of CD34+ bone marrow cells. The aim is to develop this local biobank to a world-unique resource open to MDS-interested researchers at KI and elsewhere. The dataset is also focus for well-established international collaboration. The second Nordic NMDSG14B study with HERM PI Magnus Tobiasson as principal investigator and EHL as sponsor started in 2022 and will include 200 patients.  The hypothesis is that intervention at minimal residual disease (MRD) relapse will reduce the number of clinical relapses and improve outcome after allogeneic stem cell transplantation for MDS. The experimental part of my research program focuses on SF3B1 mutated MDS with ring sideroblasts (MDS-RS) and consists of detailed studies of hematopoietic stem and progenitor cells, aberrant splicing, and mechanisms underlying clonal competition at the stem cell level. Current projects aim to understand the mechanisms behind the slow but steady clonal expansion of mutated HSC and explore the possibility to harness neoantigens and novel niche factors to counteract this expansion at an early stage, thereby preventing patients from developing transfusion dependency. Main collaborators outside KI are The Nordic MDS Group, Elli Papaemmanuil (New York) and Elsa Bernard (Paris), Mario Cazzola and Luca Malcovati (Pavia), and past and present HERM guest professors Seishi Ogawa (Kyoto) and Marc Raaijmakers (Erasmus). 

Main achievements and discoveries  

In 1984 I founded the Nordic MDS Group, which has largely contributed to diagnostic development and improved treatment. I am a key contributor to the ICC classification of MDS 2022, and the recent IPSS Molecular risk scoring system. I have led the development of European MDS guidelines and lead the International MDS guideline project. NMDSG has over the years performed a large number of academic clinical trials leading to current treatment recommend-dations; erythropoietin+G-CSF for the anemia of lower-risk MDS; the role of TP53 mutations in del(5q) MDS; and azacytidine in higher-risk disease.  The recently published NMDSG14B Part I study shows that personalized assessment of minimal residual disease (MRD) after allogeneic stem cell transplantation is clinically feasible and that MRD is a strong predictor for relapse and survival (Tobiasson, et al, 2023).  Recent studies using the MDS database have shown that DNA and RNA sequencing provide synergistic information in patients with MDS-RS (Todisco, et al, 2023) and that manifest transfusion need is a strong adverse prognostic factor. Currently, the 500 patients with combined sequencing and advanced clinical data are undergoing analyses in several projects.  We have continued to explore mechanisms for ineffective erythropoiesis and progressive anemia in MDS-RS. We were first to describe the concept of mitochondria-mediated apoptosis and contributed to the discovery of SF3B1 driver mutations in this MDS subclass.  We identified hemopoietic stem cells (HSC) as the origin of these mutations and showed that worsening anemia reflects the proportion of residual wildtype HSC. During the last period we have developed a unique method to isolate RS, allowing us to characterize the entire line of erythroid differentiation from HSC to RS and erythrocyte by single-cell DNA and RNA sequencing, proteomics and functional analyses (Moura, et al, 2023). This has given us completely novel insights into mechanisms behind clonal competition now used as a basis for current studies.

Group leader

Eva Hellström Lindberg is a double specialist in hematology and internal medicine since 1993, and Professor of hematology at the Department of Medicine, Huddinge since 2009. She has worked within the translational research field for many years and been actively involved in strategic research questions.

Eva has been president for European Association of Hematology as well as for Swedish Society of Hematology and is a member of the Nobel Assembly at the Karolinska Institutet.

Publications

Selected publications

Funding

  • Knut and Alice Wallenberg Foundation
  • The Swedish Cancer Society
  • The Scientific Research Council
  • Stockholm County Council Research funds
  • Cancer Society in Stockholm

Members and contact

Group leader

All members of the group