Johanna Ungerstedt group – Chronic myeloid malignancies

Ungerstedt lab is a translational hematology lab focusing on epigenetics and genetics in the pathobiology of myeloid hematological malignancies, especially chronic myelomonocytic leukemia and systemic mastocytosis, in search for prognostic tools and novel therapeutic targets.

Johanna Ungerstedt's research group. Photo: Private

A common feature of myeloid hematological malignancies, especially chronic myelomonocytic leukemia and systemic mastocytosis, is an overall poor prognosis and no curative treatment options. Our goal is to identify novel treatment targets and initiate and facilitate clinical trials, in order to improve symptom control and prolong survival. For the rare diagnosis Systemic Mastocytosis, we have a unique opportunity to include patients in clinical trials and collect samples, as JU is the responsible hematologist for Center of Excellence Systemic Mastocytosis, Karolinska University Hospital, and clinically manages a large part of SM patients in Sweden.

About our research

Focus area 1: Systemic Mastocytosis (SM)

SM is a care myeloid disease where almost all patients have a mutation (D816V) in the KIT tyrosine kinase receptor is, rendering mast cells constantly active. In most cases, patients experience an indolent disease with symptoms of mast cell activation that may per se be severe, but have a normal life expectancy. However, 10-15% of patients will have an aggressive course of disease with a survival of only 2-4 years. Thus, there is a large discrepancy in clinical course, and what factors determine the fate of indolent or aggressive, is largely unknown.

One main goal with our SM research is to map the genetic and epigenetic factors that contribute to determine the disease course and prognosis. By functional and structural comparison of healthy and SM cell subsets, we hope to identify novel treatment targets. We are also involved in clinical trials as well as epidemiological studies and work with disease awareness, as SM is likely underdiagnosed in Sweden. Our Center of Excellence SM collaborates closely with the second Center in Sweden at Akademiska Hospital in Uppsala, and with the European Competence Network on Mastocytosis (ECNM).

Focus area 2: Chronic Myelomonocytic Leukemia (CMML)

CMML is a heterogenous clonal myeloid stem cell disorder. The heterogeneity of disease has many aspects, one is that the life expectancy of a CMML patient is 1-120 months and there are no solid prognostic scores to predict who will be a long-time survivor and who will not, which is of course a considerable clinical problem.

Our projects focus on one hand on population based epidemiological studies of the Swedish and more in detail the Stockholm CMML patients, to understand the biology of disease and its connection to external and internal factors, e.g. inflammation. Our other focus is to conduct large scale molecular sequencing of both genetic profile (whole exome sequencing and transcriptome) and epigenetic profiles. We are also molecularly studying how inflammation is involved in initiation and progression of CMML, especially the role of dysfunctional monocytes and plasmacytoid dendritic cells.

Keywords

Epigenetics, chromatin, systemic mastocytosis, chronic myelomonocytic leukemia

Group leader

Johanna Ungerstedt

Affiliated to research
H7 Department of Medicine, Huddinge

Johanna Ungerstedt started her research group in 2012. Johanna is Associate Professor of Hematology, Specialist in Hematology and Internal Medicine. She holds a Clinical Cancer Research Position from Cancerfonden 2018-23.

She received a PhD at Karolinska Institutet in 2003 and went for post doc in Cell Biology at Memorial Sloan Kettering Cancer Center, working with histone modifying drugs. She did her second post doc in Biochemistry, MBB at Karolinska Institutet.

Group members

Kajsa Ax

Laboratory manager
H7 Department of Medicine, Huddinge

Kajsa Ax is Biomedical analyst and Lab manager, responsible for biobanking of clinical samples and for the Systemic Mastocytosis biobank.

Matilda Kjellander Kynning

Clinical assistant
H7 Department of Medicine, Huddinge

Matilda Kjellander is MD, AT doctor. She is PhD student working on CMML genetics and epidemiological studies, funded by a CSTP grant.

Ebba Westerberg

MD. PhD student.

Ebba Westerberg Lundin is MD. Resident in Hematology. Her PhD project is on autoimmune and inflammatory aspects of CMML including disturbances in the bone marrow microenvironment.

Liselotte Vesterlund

Affiliated to research
H7 Department of Medicine, Huddinge

Liselotte Vesterlund is MD, PhD. Researcher, affiliated to Johanna Ungerstedt group.

Alumni

Research support

  • The Swedish Cancer Society (Cancerfonden) Junior Clinical Research Position, 6 years 2018-23 for J Ungerstedt
  • The Swedish Cancer Society (Cancerfonden)
  • Stockholm Cancer Association (Radiumhemmets Forskningsfonder)
  • KI Clinical Scientist Training Program (CSTP), salary funding for PhD of Matilda Kjellander 2017-2022
  • Svenska Läkaresällskapet, post doc project funding for Stina Söderlund

Selected publications

Link to all publications (PubMed)

  1. A proteomic and transcriptomic screening demonstrates increased mast cell-derived CCL23 in systemic mastocytosis. Söderlund S, Boey D, van Midden W, Kjellander M, Axe K, Qian H, Dahlin JS, Ungerstedt J. J Allergy Clin Immunol 2023 Feb 20. Online ahead of print. PMID: 36813186

  2. Clinical Outcomes of Adults with Systemic Mastocytosis: A 15-Year Multidisciplinary Experience. Ungerstedt J, Ljung C, Klimkowska M, Gülen T. Cancers (Basel). 2022 Aug 16;14(16):3942-53

  3. Prognostic scoring systems and comorbidities in Chronic Myelomonocytic Leukemia: a nationwide population-based study. Moreno Berggren D, Kjellander M,, Backlund E, Engvall M, Garelius H, Lorenz F, Nilsson L, Rasmussen B, Lehmann S, Hellström-Lindberg E, Jädersten M,Ungerstedt J, Ejerblad E. Br J Haematol. 2021 Feb;192(3):474-483

  4. Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease. M Tobiasson, H Abdulkadir, A Lennartsson, S Katayama, F Marabita, A De Paepe, M Karimi, K Krjutskov, E Einarsdottir, MGrövdal, M Jansson, A Ben Azenkoud, L Corddedu, S Lehmann, K Ekwall, J Kere, EHellström-Lindberg, J Ungerstedt. Oncotarget. 2017 Apr 25;8(17):28812-28825

  5. Histone deacetylase inhibitor SAHA mediates epigenetic silencing of KIT D816V mutated systemic mastocytosis primary mast cells and selective apoptosis of mutated mast cells. K Lyberg, H Abdulkadir Ali, J Grootens, M Tirfing, H Hägglund, G Nilsson, J S Ungerstedt Oncotarget 2017 Feb 7;8(6):9647-9659

 

 

 

 

JU
Content reviewer:
26-04-2023