Cellular and molecular mechanisms promoting establishment and propagation of leukemic stem cells – Petter Woll group

The group studies cellular and molecular mechanisms promoting establishment and propagation of leukemic stem cells. We wish to understand the cellular and molecular targets for highly recurrent mutations in hematologic malignancies, in order to prevent leukemia and treat the patient.

A group of people in front of Aula Medica in Solna.
Petter Woll's research group at The Department of medicine Huddinge. Photo: Stefan Zimmerman

About our research

The Petter Woll lab is located at the Center for Hematology and Regenerative Medicine (HERM) in Neo, KI Campus Flemingsberg.

Mission of the research group

Cancer typically develops through the sequential acquisition of genetic lesions targeted to cells in normal tissues. Although most cells have a short lifespan and gradually are lost over time, tissue-specific stem cells such as the hematopoietic stem cell, with ability to sustain throughout the lifespan of an individual are at particular risk for malignant transformation due to the random accumulation of DNA mutations. 

Next-generation DNA sequencing has revealed the genetic architecture of myeloid malignancies and demonstrated that most chronic myeloid malignancies are driven by recurrent oncogenic mutations targeted to a limited number of genes. The same mutations can be detected in a large fraction of blood cells in healthy, elderly individuals, without any symptoms of hematologic disorders but with higher risk for later leukemic transformation, a condition referred to as clonal hematopoiesis (CH). 

Our long-term goal is to exploit presence of somatic non-driver and driver mutations targeted to hematopoietic stem cells to provide new insight toward normal human hematopoietic stem cell biology, transformation allowing development of leukemic stem cells and develop strategies for therapeutic targeting of pre-leukemic and leukemic stem cells. This is achieved by combining advanced flow cytometry identification and isolation of distinct bone marrow hematopoietic stem and progenitor cells from healthy individuals and patients with leukemia, with DNA sequencing of for identification of somatic mutations. This allows for genetic fate mapping to monitor the contribution of mutations originating from hematopoietic stem cells to steady state hematopoiesis, as well as following stress and exposure to extrinsic cues by tracking changes in mutation contribution of human bone marrow cells transplanted into immune-compromised mice. Detailed cellular and molecular characterization of candidate leukemia propagating cells has also identified potential targets for therapeutic targeting, which is explored in in vitro and in vivo assays in combination with immune cell-based therapeutics. Collaborators include Sten Eirik Jacobsen (KI), Eva Hellström-Lindberg (KI), Johanna Ungerstedt (KI), Magnus Tobiasson (KI), Rickard Sandberg (KI), Sten Linnarsson (KI), Seishi Ogawa (Kyoto University), Adam Mead (University of Oxford), Johanna Olweus (University of Oslo). 

Collaborators

Karolinska Institutet

International collaborations

  • Johanna Olweus, Department of Cancer Immunology, Oslo University Hospital
  • Adam Mead, MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford

Research support

  • Cancerfonden
  • Radiumhemmets Forsknings Fonder
  • Ming Wai Lau Centre for Reparative Medicine 

Publications

Selected publications

Members and contact

Group leader

All members of the group

FACS Facility

Belinda Reinhold Pannagel

Research technician
+46852483989
Department of Medicine, Huddinge
Profile image

Narmadha Subramanian

Research technician