Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults and generally a disease of older people. More effective and safer treatments are greatly needed since AML has the worst survival rate of adult leukemias.
In his doctoral thesis, M.Sc. Jarno Kivioja focused on a specific genetic subtype of AML with chromosomal rearrangement involving chromosomes 5 and 11. This rearrangement juxtaposes nucleoporin 98 (NUP98) and nuclear receptor binding SET-domain protein 1 (NSD1) genes together.
The prognosis of this subgroup of leukemia patients is highly unfavorable. Therefore, the main objective of Jarno’s thesis entitled “The NUP98-NSD1 Fusion Gene in Acute Myeloid Leukemia” was to facilitate molecular detection and treatment of AML patients with this rearrangement.
Jarno graduated from the Faculty of Biological and Environmental Sciences of the University of Helsinki in 2012. He wanted to continue with his doctoral studies in a group focusing on precision medicine in cancer and identified the research done in Caroline Heckman’s group at FIMM as an exciting possibility. A few months later, he started his thesis project in the context of the FIMM’s Individualised systems medicine in cancer (ISM) Grand Challenge programme, in collaboration with Professor Kimmo Porkka, who is Jarno’s co-supervisor.
The working atmosphere at FIMM is very dynamic and collaborative and the high level of the technologies and expertise available in house has really enabled me to carry out my projects.
- Jarno Kivioja
Jarno’s thesis consists of two extensive first-author publications. In the first subproject, he identified a novel transcript variant that can be used for detecting the fusion gene more accurately from newly diagnosed patients and after the patients have been treated (called minimal residual disease).
From my perspective, it is extremely important to be able to detect even the smallest number of leukemic cells left after treatment. That would enable clinicians to start investigational treatments before hematological relapse occurs and would improve the chances of long-term survival.
In the second publication, Jarno combined data from high-throughput drug sensitivity and resistance testing with RNA sequencing with the aim of identifying novel effective compounds for AML patients having the NUP98-NSD1 fusion gene and concurrent FLT3-ITD mutation.
In addition to the technologies available at FIMM, Jarno generated mouse cell models carrying the leukemia mutations of interest. For this, he spent two months in Switzerland. After screening over 300 anti-cancer compounds on patient cells and the generated mouse cell models, he was able to show that the cells were highly sensitive to drugs dasatinib and navitoclax. These drugs were especially effective when given in combination, suggesting that a combination therapy might offer a clinically relevant treatment strategy for these patients.
In his earlier years, Jarno was a professional athlete competing in pole vaulting. Different sports activities still are very important part of his daily life.
There are many similarities between becoming an elite athlete and an independent researcher. Both require determination, perseverance, an ability to learn from setbacks and, very importantly, good mentors.
Jarno will continue working at FIMM until the end of the year to finish his ongoing projects and to settle his next career move. In the future, he would like to continue working with translational cancer medicine, perhaps in pharmaceutical industry.
The public examination of M.Sc. Jarno Kivioja’ doctoral dissertation will take place on 31 May at 12 o’clock noon in Biomedicum Helsinki lecture hall 2, Haartmaninkatu 8. Associate Professor Linda Fogelstrand, Sahlgrenska University Hospital, Gothenburg, will serve as the opponent, and Professor Kari Keinänen as the custos.
The dissertation is available in an electronic form.