Riikka Karjalainen's dissertation provides new clues on drug resistance in acute myeloid leukemia

Riikka Karjalainen’s thesis entitled "Studies on Drug Resistance and Molecular Biomarkers in Acute Myeloid Leukemia” will be publicly examined on Friday, 4th of October, with the permission of the Faculty of Medicine of the University of Helsinki.

Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. The disease has a poor prognosis and most of the AML patients suffer from relapse after cancer treatment.  

In her doctoral thesis, M.Sc. Riikka Karjalainen focused on investigating the biology of this devastating disease. The main objectives of her thesis were to identify novel mechanisms leading to drug resistance and biomarkers that could be used to predict its development.

Riikka graduated from the Department of Biochemistry of the University of Oulu in 2010. After working in France for a year, she wanted to continue with her doctoral studies in a group focusing on cancer precision medicine. At the time, FIMM’s Individualized systems medicine in cancer (ISM) Grand Challenge programme was recruiting several PhD students. Riikka got one of these positions and started her thesis project in Caroline Heckman’s group in collaboration with Professor Jonathan Knowles, who is Riikka’s co-supervisor.

It was very exciting time to start the thesis project with so many FIMM researchers and clinicians working together to achieve something that we felt was completely new and game changing!

- Riikka Karjalainen

Riikka’s thesis consists of three publications. In the first subproject, she tested the efficacy of more than 300 drugs against AML cells in stromal cell-conditioned medium and compared the data to results achieved using standard cell culture medium. The results demonstrated that the stroma-derived growth factors altered the response of many tested drugs.

Importantly, the stromal conditions significantly reduced the sensitivity of the AML cells to a promising new AML drug venetoclax that was recently approved for the treatment of newly diagnosed, elderly AML patients. Venetoclax is an inhibitor of the anti-apoptotic protein BCL-2. Further experiments showed that the stroma induced resistance to venetoclax can be overcome by inhibition of JAK/STAT signaling.

During this study, we also learned a lot about the importance of cancer microenvironment and optimization of AML cell culture conditions. This knowledge is now utilized in the experiments performed by our research group and the FIMM Technology Centre.

In the two other publications, Riikka combined different types of data sources with the aim of identifying novel biomarkers for AML or venetoclax resistance.  By applying machine learning methods for drug sensitivity and resistance testing and gene expression data, high expression of two calcium binding family genes were found as promising new biomarkers for venetoclax resistance. Moreover, the subproject done in collaboration with Tero Aittokallio’s group led to a discovery of AML protein biomarkers.

During her thesis project, Riikka has used a large number of different techniques and performed complex laboratory experiments. In addition to the technologies available at FIMM, she, with the help of collaborators in Bergen, did functional studies with mouse models. When asked about her personal characteristics that have helped her during the thesis years, Riikka mentions scientific curiosity, perseverance, and the famous Finnish sisu. With roots in the Kainuu region, she is accustomed to working hard to receive her goals.

Riikka will stay at FIMM to finish her new project focusing on optimization of lymphoma cell culture conditions. In the future, she would like to continue working with cancer medicine, either as a post-doctoral researcher or in the pharmaceutical industry.

The public examination of M.Sc. Riikka Karjalainen’s doctoral dissertation will take place on 4th of October at 12 o’clock noon in Porthania, lecture room PIII, Yliopistonkatu 3. Dr. Eva Szegezdi, National University of Ireland, Galway, will serve as the opponent, and Professor Kimmo Porkka as the custos.

The dissertation is also available in electronic form through the E-thesis service.