Heikki Kuusanmäki's dissertation verifies the importance of cell survival signaling pathways in leukemia

Heikki Kuusanmäki’s thesis entitled "Targeting Key Survival Signaling Pathways for The Treatment of Leukemia” will be publically examined on Friday, 28 September, with the permission of the Faculty of Medicine of the University of Helsinki.

Despite recent advances in leukemia genetics, transforming this new knowledge into clinically actionable strategies has been challenging. In his doctoral thesis, M.Sc. Heikki Kuusanmäki has approached this problem by combining genetic profiling with high-throughput drug sensitivity testing in patient derived leukemia cells.

The main aim of his thesis entitled “Targeting Key Survival Signaling Pathways for The Treatment of Leukemia” was to identify novel driver mutations in two rare leukemia types, large granular lymphocyte (LGL) leukemia and T-cell acute lymphoblastic leukemia (T-ALL). Furthermore, he wanted to develop a new flow cytometry-based drug screening assay to assess cell population specific drug responses in heterogenous leukemia samples. 

Heikki graduated from the Translational medicine (TRANSMED) research programme of the University of Helsinki in 2013. For his Master’s project, he wanted to find a lab where state-of-the-art technologies and translational research could be combined and decided to contact Caroline Heckman, a group leader at FIMM.

"The research environment at FIMM was as vibrant and stimulating as I was hoping and after finishing my Master’s project I was pleased to continue working towards a Ph.D", said Heikki Kuusanmäki.

Heikki’s thesis project has been conducted in the context of the FIMM’s Individualised systems medicine in cancer (ISM) Grand Challenge programme, in collaboration with Professor Satu Mustjoki‘s group. The thesis consists of three publications published in esteemed oncology journals and one manuscript that is currently under review.

In the first two subprojects of his thesis, Heikki utilised exome sequencing and identified novel activating mutations in the STAT5B gene both in LGL and in T-ALL leukemia patients. This gene was of special interest, since the group had earlier shown that mutations in a related gene, STAT3, are the main drivers in LGL leukemia.

In the third publication, high-throughput drug sensitivity testing was used with the aim of identifying compounds that could inhibit mutant STAT3 activity. Among the more than 300 screened compounds, Hsp90 inhibitors were shown to effectively reduce both the mutant and the wildtype STAT3 activity.

The last subproject of the thesis focused more on technology development. The cell viability assays used to monitor drug response are fast and robust but cannot accurately measure cell population specific drug responses.

This last study is definitely my personal favorite. Because of the limitations of the conventional assays we used I had a feeling that we were missing important information. It took me several years to develop and streamline the flow cytometry-based drug screening assay but now we are able to accurately assess cell population specific drug responses in heterogenous leukemia samples.

I believe that the blast specific drug sensitivity results we can now produce have increased predictive accuracy to treatment outcome.

- Heikki Kuusanmäki

Heikki’s future plans are not yet settled but he would like to continue working with translational cancer medicine, either as a post-doc or in pharmaceutical industry.

I have always been motivated by the research itself, especially when I know that the work we do can have a great impact on patients’ lives. Having a job with meaning is a privilege.

The public examination of M.Sc. Heikki Kuusanmäki’s doctoral dissertation will take place on 28 September at 12:00 in Children’s Hospital Niilo Hallman lecture hall, Stenbäckinkatu 11. Professor Jukka Westermarck, Turku Centre for Biotechnology, University of Turku, will serve as the opponent, and Professor Satu Mustjoki as the custos.