Olli Lohi is investigating the causes of childhood leukaemia and novel therapies

Submitted on Wed, 04/26/2017 - 17:50
Dosentti Olli Lohi
Docent Olli Lohi is working with childhood leukaemia as both a physician and a researcher. “We use samples collected from patients in our research. Questions arising from clinical medicine can thus be studied more accurately in the laboratory,” he says.


Only two research groups in Finland are conducting basic research on childhood leukaemia. One of them led by Docent Olli Lohi is working at the University of Tampere. Lohi and his research group has discovered that specific transcriptional features partly explain the occurrence of genetic lesions in leukaemia. The group has also discovered a drug that seems to be effective in about one-third of T-cell leukaemia patients.

 “We are looking at the basic biological and mechanistic reasons for what causes leukaemia and why the disease does not necessarily react as expected to medicines," Lohi explains.

“The second main line of research is that we are trying to discover novel therapies for the leukaemia cases that have a worse prognosis,” Lohi says.

The research group currently employs four full-time and two part-time researchers who are simultaneously working on several distinct topics.

Research is approaching the causes of the disease

“In 2016, we published two studies where we were practically for the first time able to chart the transcriptional causes of the most frequent subtype of childhood acute lymphoblastic leukaemia (ALL),” Lohi says.

The study published in the journal Genome Research showed that the fusion transcription factor prevalent in ALL represses genes that are needed for the normal differentiation of B-lymphocytes from the stem cells in the bone marrow.

Leukaemias, like other cancers, are not caused by just one mutation; there must be several. When a sufficient number of genetic defects occurs in the same cell, leukaemia may occur.

“In our second study, we identified transcriptional features that associate with recurrent mutations in leukaemias. When transcription slows down, DNA in these genomic loci become temporarily vulnerable to the damaging activities of certain cellular enzymes,” Lohi explains.

Lohi regards this study published in the journal eLife as a significant achievement in his leukaemia research.
Another article about discovering a personalised drug for T-cell leukaemias is now under the review process. The drug seems to be effective in about one-third of this type of cancer, which is more fatal than other types of leukaemia especially when relapsing.
 

Working as a physician and a researcher

Olli Lohi has a long record of researching cancer; the disease was the topic of his doctoral dissertation in 1998.
After specialising in paediatrics, Lohi became interested in childhood blood diseases and cancer and completed a further education programme. He says that he did not start researching leukaemia until the 2010s.

“In my work as a physician, I treat children with cancer, which means that there is a direct link to the research I am conducting. Leukaemia is the most common cancer in children,” says Lohi who is the Chief Physician of the unit for paediatric haematology and oncology at Tampere University Hospital.

Technological development opens new opportunities

Studies progress on the terms of research.

“When you are researching a particular topic, many other aspects also start to look interesting, and you often come up with new ideas for further analysis. On the other hand, many lines of research end in us realising that they are not worth following through,” Lohi explains.

“Research gets you carried away; it always opens new routes and possibilities. It may well be that the original idea was different and the picture changes as we move forward. The process continues on the terms of research,” Lohi describes.

“It is fascinating because you are always dealing with previously uncharted territory,” he continues.
Developing technology opens new opportunities

“What we are doing today would not have been possible ten years ago,” Lohi says.

“Similar questions were already posed over twenty years ago, but the opportunities for finding answers are much better now. For example, there have been previous attempts to find the mechanisms of the most common childhood cancer about which we published the article last year. The technologies and methods have developed so much that it is now easier to answer many such questions,” Lohi explains.

Cooperation furthers research

Lohi emphasises the role of research cooperation.

“My research group has participated in the creation of a sizable gene expression database on leukaemias and other blood cancers,” Lohi says.

Although the study report on the database is still under the review process for publication, the database has already been used. Lohi finds it a great tool.

“Particularly in this work – but also in other studies – we have greatly benefitted from cooperation with Docent Merja Heinäniemi’s research group at the University of Eastern Finland in Kuopio,” Lohi says.

Heinäniemi leads the other Finnish research group engaged in basic research on childhood leukaemia at the University of Eastern Finland.

“In practice, my group and Heinäniemi’s work on largely the same themes. They do a lot of research on bioinformatics and computational aspects and we conduct a lot of experimental research on the same issues. The third link contributing to the advancement of leukaemia research is Professor Matti Nykter who is a bioinformatics researcher at the University of Tampere.

Lohi is also engaged in international cooperation with research groups in Sweden, other European countries and the United States.

“Networking is extremely important because it advances so many things. The help offered in such networks is reciprocal. It is also good for the University of Tampere in general that researchers travel the world and spread the word about our university,” Lohi continues.

Drug trials centre may provide a treatment option

Lohi was instrumental in establishing PeeTU, the Paediatric Early Phase Trials Unit for clinical drug development at Tampere University Hospital.

The unit investigates medicines that are already used on adults and new drugs that are just entering the market.

“The idea is to find a biologically meaningful treatment alternative for children and adolescents with recurring cancer for whom we can no longer provide therapies that cure,” Lohi says.

Demanding and fascinating work

Lohi estimates that he works for 50 – 55 hours per week.

“Working as a physician is demanding as such, but research is fascinating in a different way. I have had the good fortune to get external funding so I am able to periodically concentrate just on research,” Lohi says.

“When I conduct research on a topic that is the same as in my clinical work, both serve each other extremely well. In addition, I am able to form very significant networks through research, which directly benefit my work with patients,” Lohi says.

The largest individual funder of Lohi’s work is Jane and Aatos Erkko Foundation. He has also received research grants from the Foundation for Pediatric Research, the Academy of Finland, Cancer Society of Finland, Cancer Society of Pirkanmaa and Väre Foundation for Pediatric Cancer Research.

Olli Lohi received the University of Tampere’s Annual Research Award on 26 April 2017

Text: Pirjo Achté
Photo: Jonne Renvall