Samuli Eldfors' dissertation demonstrates the clinical significance of somatic mutations in leukemias

The aim of M.Sc. Samuli Eldfors’ thesis entitled “Analysis of somatic mutations in leukemias” was to identify clinically important somatic mutations contributing to the development and treatment response of different leukemias.

The fast development in the field of cancer genetics has been driven by rapid advances in sequencing technology. The ability to sequence tumor DNA routinely has a fundamental impact on cancer research and clinical diagnosis since genetic mutations are the best molecular markers to diagnose and characterize cancers.

The aim of M.Sc. Samuli Eldfors’ thesis entitled “Analysis of somatic mutations in leukemias” was to identify clinically important somatic mutations contributing to the development and treatment response of different leukemias. His doctoral dissertation was publically examined on Monday, 21 May, with the permission of the Faculty of Biological and Environmental Sciences of the University of Helsinki.

Samuli graduated from the University of Helsinki in 2004 with M.Sc. in Biochemistry. Before joining FIMM, he worked at the Institute of Biotechnology, University of Helsinki and the EMBL-European Bioinformatics Institute in Cambridge, UK. In 2010 he was offered a bioinformatician position at FIMM Technology Centre and soon after that, he started to concurrently work on his Ph.D. in Caroline Heckman’s research group. The thesis has been co-supervised by Professor Olli Kallioniemi.

Samuli’s thesis project has been conducted in the context of the FIMM’s Individualised systems medicine in cancer (ISM) Grand Challenge programme. In the thesis, Samuli has identified somatic mutations in three leukemia types and analyzed the biological and clinical significance of these mutations. A major part of the work has been the development of a computational workflow and the application of bioinformatics approaches to detect mutations based on whole exome sequencing data. These pipelines have become key components of the ISM research programme.

Samuli’s thesis consists of two publications published in esteemed journals and one manuscript that is currently under review.

In the first study of the thesis, STAT3 mutations were identified to be the main driver mutations in large granular lymphocytic (LGL) leukemia. This gene is mutated in almost 40% of LGL patients and these mutations can now be used as diagnostic biomarkers to differentiate this disease from other forms of T-cell lymphocytosis.

In the second publication, Samuli analyzed both NGS and drug sensitivity data in a relapsed patient with a rare leukemia type, B-cell precursor acute lymphoblastic leukemia. The patient had a specific chromosomal translocation which results in the TCF3-PBX1 gene fusion. The patient’s leukemia was shown to be sensitive to a drug called idelalisib, indicating that this drug is a promising treatment option for relapsed patients with this leukemia type.

The STAT3 mutation study was a scientific jackpot since the first mutation was detected in a patient that was the very first leukemia patient we sequenced at FIMM. The key discoveries in the second publication of the thesis were made initially by in-depth analysis of a single patient case. Professor Kimmo Porkka encouraged the PhD students working with the leukemia patient data to select patient cases to focus on in order to understand the disease biology in-depth.

- Samuli Eldfors

I have learned that in the field of personalised medicine, one patient can prove to be extremely valuable, as long as there is a way to validate the findings.

In the third study, Samuli focused on identifying mutations in relapsed acute myeloid leukemia patients. The identified mutations provide insight into the biology of therapy resistance in acute myeloid leukemia and are potential biomarkers that can be used to predict response to therapy.

Through his work Samuli has been able to contribute to several studies and he has an impressive track record of more than 20 co-authored publications. He is rightly proud of the mutation analysis pipelines he has developed.

The data obtained by exome sequencing contains very large amounts of clinically relevant information but only a part of this information is currently systematically investigated. According to Samuli, a major remaining challenge is to develop better methods for accurate identification of insertions and deletions.

A key aspect of our approach has been to share the somatic mutation information generated by exome sequencing with the clinicians treating the patients on an ongoing basis. This practice supplements clinical diagnostics and provides clinicians with a more detailed understanding of the biology of the leukemias of the patients included in the study.

 Samuli will continue working at FIMM at least until the end of the year to finish his ongoing work and to settle his next career goals.

The public examination of M.Sc. Samuli Eldfors’ doctoral dissertation took place on 21 May at 13:00 in Lecture hall 3 at Biomedicum Helsinki 1, Haartmaninkatu 8. Professor John Welch, Washington University, served as the opponent, and Professor Minna Nyström as the custos.