Linda Holmfeldt – Molecular characterization of acute leukemia
Acute leukemia is a blood disorder that is diagnosed in about 400 Swedes annually. Our research aims to increase the understanding of why many patients do not respond to treatment or suffer from a relapse of the disease. We also want to identify changes in the tumor cells that can be used to develop more efficient treatment alternatives for these high-risk leukemia types that today are associated with a very poor outcome.
Acute leukemia is characterized by an overproduction of immature white blood cells in the bone marrow that causes disease by for instance outcompeting the production of normal blood cells. Acute leukemia can be of either myeloid or lymphoid origin, depending on the type of blood cell the leukemia originated from. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, while acute lymphoblastic leukemia (ALL) is the overall most common type of cancer in children.
New treatment alternatives are needed for acute leukemia
Despite the best possible treatment with the drugs available today, a large fraction of the patients do not respond to the treatment or experience a relapse after an initial response. It is not possible to increase the survival by intensifying the treatment, since the cancer medicines available today are toxic themselves. Thus, to find new, more efficient treatment alternatives with fewer side effects, more knowledge about the leukemia onset and progression is needed.
Detailed analyses for a better understanding of AML
The cancer cells are characterized by different mutations, some of which are associated with a worse response to treatment. The reason for the varying treatment response is, however, currently unclear.
To get a better understanding of why AML very often leads to incurable relapses, we are in an unbiased way characterizing the changes occurring in the cancer cells from a large number of AML patients. We use a combination of analysis methods to get the most complete picture possible of DNA and RNA alterations in the tumour cells, as well as their protein composition. These analyses serve as the basis for a functional evaluation to identify treatable alterations in the tumour cells.
Aberrant activity of epigenetic regulators in ALL
In our previous studies of pediatric high-risk and relapsed ALL, we have identified a high frequency of mutations that affect the function of so called epigenetic regulators. These are regulators that control the activity of our genes by changing the structure of the chromosomes. To investigate how these mutations affect tumour formation and therapy resistance, we use a combination of biochemical and cellular analyses and in vivo models, which give us information about the downstream effects by mutated epigenetic regulators.