Translating genomic discoveries into improved clinical decision making, mechanistic understanding, and therapy of acute leukemia
The overall objectives of our research program are to improve clinical decision making of acute leukemia by using integrative sequencing approaches, to increase our understanding of how genetic abnormalities cause leukemia, and to identify cell surface markers on leukemia stem cells that can be used as therapeutic targets.
Background: Acute leukemia is a cancer of blood forming cells and can be divided into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) depending on the blood cell lineage affected. While AML is the most common type of acute leukemia in adults, ALL is the most common form of malignancy in children. With current treatment protocols, consisting mainly of cytostatic drugs, the overall five-year survival in AML is less than 30% (in elderly patients less than 10%). Pediatric ALL is associated with an excellent overall prognosis, but the intense treatment may cause severe side effects, calling for new directed therapies with less toxicity. Acute leukemia is caused by several different genetic changes (mutations) occurring in a hematopoietic stem cell. To increase the understanding of why these malignancies develop and to improve clinical decision-making, there is a need to identify the underlying mutations in the leukemic cells of each patient at diagnosis. New technological development, in particular in sequencing the genomes of cancer cells, offers new hopes in improving diagnostics, treatment selection, and follow up of patients affected by acute leukemia, but clinical implementation of modern genomic technologies are lagging behind recent research efforts. Current treatment regiments mainly affect the more mature leukemic cells, leaving the leukemia stem cell pool intact that eventually will regrow and cause disease relapse. Thus, there is a great demand to identify targets on the leukemia stem cell towards which new drugs could be targeted.
Research projects: In our research group, the genomes of leukemic cells of newly diagnosed patients with acute leukemia are comprehensively characterized by integrative sequencing approaches and key findings are translated into in a clinical diagnostic setting to improve clinical decision making. In addition, newly discovered mutations are functionally studied to elucidate how such alterations cause leukemia and studies are performed to identify new targets on leukemia stem cells against which antibodies will be generated. A third project is focused on providing proof of concept for an antibody-based therapy in relevant disease models.
The team: You will be joining a strong and dynamic translational research team working all the way from identifying genetic alterations in acute leukemia by the most modern sequencing technologies, to advanced functional studies of newly identified mutation and the identification of novel targets for improved therapies.