- With spatial tissue analysis, we demonstrate that the intratumoral and peritumoral regions of ccRCC patients represent distinct immunological profiles and are associated with clinical phenotypes.
Dufva O, Pölönen P, Brück O, Keränen MAI, Klievink J, Mehtonen J, Huuhtanen J, Kumar A, Malani D, Siitonen S, Kankainen M, Ghimire B, Lahtela J, Mattila P, Vähä-Koskela M, Wennerberg K, Granberg K, Leivonen SK, Meriranta L, Heckman C, Leppä S, Nykter M, Lohi O, Heinäniemi M, Mustjoki S. Immunogenomic Landscape of Hematological Malignancies. Cancer Cell. 2020;38(3):380-99.e13.
- Exploration of large-scale genomic datasets links immune regulation with cancer subtypes and genomics across hematological malignancies
- Characterization of immune cell contexture in adult ALL bone marrow microenvironment. High proportion of CD4+PD1+TIM3+ T cells predicted poor survival.
– The immune landscape in CML bone marrow is immunosuppressed at diagnosis and can be partially reset with TKI treatment. Immune profiles can be used to predict treatment responses.
Lundgren S, Keränen MAI, Kankainen M, Huuhtanen J, Walldin G, Kerr CM, Clemente M, Ebeling F, Rajala H, Brück O, Lähdesmäki H, Hannula S, Hannunen T, Ellonen P, Young NS, Ogawa S, Maciejewski JP, Hellström-Lindberg E, Mustjoki S. Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia. Leukemia. 2021 May;35(5):1365-1379.
- Somatic mutations in in expanded T cell clones were discovered in patients with immune-mediated aplastic anemia. T cells with somatic mutations on JAK-STAT and MAPK pathway genes were characterized by single-cell transcriptomics.
– Discovery of clonal LGL expansion as an off-target effect of targeted leukemia therapy.
Flanagan SE*, Haapaniemi E*, Russell MA*, Caswell R, Lango Allen H, De Franco E, McDonald TJ, Rajala H, Ramelius A, Barton J, Heiskanen K, Heiskanen-Kosma T, Kajosaari M, Murphy NP, Milenkovic T, Seppanen M, Lernmark A, Mustjoki S, Otonkoski T, Kere J, Morgan NG, Ellard S & Hattersley AT. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nature Gen. 2014, 46, 812-814.
*Equal contribution
– Discovery of clonal T- and NK-cells in untreated leukemia patients.
– Discovery of somatic mutations in patients with AA and MDS.
Rajala HL, Eldfors S*, Kuusanmaki H*, van Adrichem AJ, Olson T, Lagstrom S, Andersson EI, Jerez A, Clemente MJ, Yan Y, Zhang D, Awwad A, Ellonen P, Kallioniemi O, Wennerberg K, Porkka K, Maciejewski JP, Loughran TP, Jr., Heckman C, Mustjoki S. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013 Apr 17.
*Equal contribution
– This was the first time to discover somatic mutations in STAT5 gene. The mutation type also correlated with clinical disease phenotype.
Koskela HL*, Eldfors S*, Ellonen P, van Adrichem AJ, Kuusanmaki H, Andersson EI, Lagstrom S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM, Almusa H, Edgren H, Lepisto M, Mattila P, Guinta K, Koistinen P, Kuittinen T, Penttinen K, Parsons A, Knowles J, Saarela J, Wennerberg K, Kallioniemi O, Porkka K, Loughran TP, Jr.*, Heckman CA*, Maciejewski JP*, Mustjoki S. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366:1905-13.
*Equal contribution
– Groundbreaking observation demonstrating that LGL leukemia is caused by activating STAT3 mutations.
Drug screening and personalized medicine
Malani D, Kumar A, Bruck O, Kontro M, Yadav B, Hellesoy M, Kuusanmaki H, Dufva O, Kankainen M, Eldfors S, Potdar S, Saarela J, Turunen L, Parsons A, Vastrik I, Kivinen K, Saarela J, Raty R, Lehto M, Wolf M, Gjertsen BT, Mustjoki S, Aittokallio T, Wennerberg K, Heckman CA, Kallioniemi O, Porkka K. Implementing a functional precision medicine tumor board for acute myeloid leukemia. Cancer Discov. 2021 Nov 17:candisc.0410.2021.
- Morphologic features found in the bone marrow of MDS and MDS/MPN patients are associated with genetic and cytogenetic alterations, prognosis and patient demographics.
– JAK-STAT signaling importantly contributes to the pathogenesis of the extremely aggressive natural killer cell leukemia.
Andersson EI, Pützer S, Yadav B, Dufva O, Khan S, He L, Sellner L, Schrader A, Crispatzu G, Oleś M, Zhang H, Adnan-Awad S, Lagström S, Bellanger D, Mpindi JP, Eldfors S, Pemovska T, Pietarinen P, Lauhio A, Tomska K, Cuesta-Mateos C, Faber E, Koschmieder S, Brümmendorf TH, Kytölä S, Savolainen ER, Siitonen T, Ellonen P, Kallioniemi O, Wennerberg K, Ding W, Stern MH, Huber W, Anders S, Tang J, Aittokallio T, Zenz T, Herling M, Mustjoki S. Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling. Leukemia. 2017 Aug 14. doi: 10.1038.
– Novel drug candidates and genetic characterization of a rare lymphocytic leukemia.
– Characterization of immunological changes during targeted kinase inhibitor therapy and their correlation with therapy response. Pan-European collaboration in clinical trial.