Publications

Selected publications.
Tumor Immunology
  1. Brück O, Lee MH, Turkki R, Uski I, Penttilä P, Paavolainen L, Kovanen P, Järvinen P, Bono P, Pellinen T, Mustjoki S, Kreutzman A. Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients. Mod Pathol. 2021 Dec;34(12):2229-2241.
    - 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.
  2. 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
  3. Dufva O, Koski J, Maliniemi P, Ianevski A, Klievink J, Leitner J, Polonen P, Hohtari H, Saeed K, Hannunen T, Ellonen P, Steinberger P, Kankainen M, Aittokallio T, Keranen MAI, Korhonen M, Mustjoki S. Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity. Blood. 2020;135(9):597-609.
  4. Hohtari, H., Brück, O., Blom, S. et al. Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL. Leukemia. 2019;33:1570–1582.
    - Characterization of immune cell contexture in adult ALL bone marrow microenvironment. High proportion of CD4+PD1+TIM3+ T cells predicted poor survival.
  5. Brück O, Blom S, Dufva O, Turkki R, Chheda H, Ribeiro A, Kovanen P, Aittokallio T, Koskenvesa P, Kallioniemi O, Porkka K, Pellinen T, Mustjoki S. Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML. Leukemia. 2018 Jun 20.
    – 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.
  6. Hekim C*, Ilander M*, Yan J, Michaud E, Smykla R, Vähä-Koskela M, Savola P, Tähtinen S, Saikko L, Hemminki A, Kovanen PE, Porkka K, Lee FY, Mustjoki S. Dasatinib Changes Immune Cell Profiles Concomitant with Reduced Tumor Growth in Several Murine Solid Tumor Models. Cancer Immunol Res. 2017 Feb;5(2):157-169.
    *Equal contribution
    – Discovery of beneficial immunomodulatory effects of dasatinib in murine solid tumor models.
  7. Mustjoki S, Auvinen K*, Kreutzman A*, Rousselot P, Hernesniemi S, Melo T, Lahesmaa-Korpinen AM, Hautaniemi S, Bouchet S, Molimard M, Smykla R, Lee FY, Vakkila J, Jalkanen S, Salmi M, Porkka K. Rapid mobilization of cytotoxic lymphocytes induced by dasatinib therapy. Leukemia. 2013 Apr;27(4):914-24.
    *Equal contribution
    – Description of rapid mobilization of lymphocytes after dasatinib intake.
  8. Kreutzman A*, Ladell K*, Koechel C, Gostick E, Ekblom M, Stenke L, Melo T, Einsele H, Porkka K, Price DA*, Mustjoki S*, Seggewiss R*. Expansion of highly differentiated CD8+ T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation. Leukemia. 2011;25:1587-97.
    *Equal contribution
    – Proof of antiviral clonal T-cells in leukemia patients during TKI therapy.
  9. Kreutzman A, Juvonen V, Kairisto V, Ekblom M, Stenke L, Seggewiss R, Porkka K, Mustjoki S. Mono/oligoclonal T and NK cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood. 2010;116:772-82.
    – Discovery of clonal LGL expansion as an off-target effect of targeted leukemia therapy.
  10. Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F, Hjorth-Hansen H, Hoglund M, Kovanen P, Laurinolli T, Liesveld J, Paquette R, Pinilla-Ibarz J, Rauhala A, Shah N, Simonsson B, Sinisalo M, Steegmann JL, Stenke L, Porkka K. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia. 2009;23:1398-405.
    – Discovery of clonal LGL expansion as an off-target effect of targeted leukemia therapy.
Somatic mutations in inflammation
  1. Mustjoki S, Young NS. Somatic Mutations in "Benign" Disease. N Engl J Med. 2021 May 27;384(21):2039-2052
  2. 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.
  3. Kim D, Park G, Huuhtanen J, Ghimire B, Rajala H, Moriggl R, Chan WC, Kankainen M, Myllymäki M, Mustjoki S. STAT3 activation in large granular lymphocyte leukemia is associated with cytokine signaling and DNA hypermethylation. Leukemia. 2021 Dec;35(12):3430-3443.
    - Investigation of functional effect of somatic STAT3 mutations in T-cell LGL leukemia.
  4. Kim D, Park G, Huuhtanen J, Lundgren S, Khajuria RK, Hurtado AM, Muñoz-Calleja C, Cardeñoso L, Gómez-García de Soria V, Chen-Liang TH, Eldfors S, Ellonen P, Hannula S, Kankainen M, Bruck O, Kreutzman A, Salmenniemi U, Lönnberg T, Jerez A, Itälä-Remes M, Myllymäki M, Keränen MAI, Mustjoki S. Somatic mTOR mutation in clonally expanded T lymphocytes associated with chronic graft versus host disease. Nat Commun. 2020;11:2770.
    - Discovery of novel somatic gain-of-function mTOR mutation in a patient with chronic graft versus host disease.
  5. Savola P, Martelius T, Kankainen M, Huuhtanen J, Lundgren S, Koski Y, Eldfors S, Kelkka T, Keranen MAI, Ellonen P, Kovanen PE, Kytola S, Saarela J, Lahdesmaki H, Seppanen MRJ, Mustjoki S. Somatic mutations and T-cell clonality in patients with immunodeficiency. Haematologica. 2019;105(12):2757-2768.
  6. Savola P*, Kelkka T*, Rajala HL, Kuuliala A, Kuuliala K, Eldfors S, Ellonen P, Lagström S, Lepistö M Hannunen T, Andersson EI, Khajuria RK, Jaatinen T, Koivuniemi R, Repo H, Saarela J, Porkka K, Leirisalo-Repo M, Mustjoki S. Somatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis. Nat Commun. 2017 Jun;21(8):15869.
    *Equal contribution
    – Discovery of novel somatic mutations in RA patients’ circulating cytotoxic lymphocytes.
  7. Andersson EI*, Tanahashi T*, Sekiguchi N, Gasparini VR, Bortoluzzi S, Kawakami T, Matsuda K, Mitsui T, Eldfors S, Bortoluzzi S, Coppe A, Binatti A, Lagström S, Ellonen P, Fukushima N, Nishina S, Senoo N, Sakai H, Nakazawa H, Kwong YL, Loughran TP, Maciejewski JP, Mustjoki S, Ishida F. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. Blood. 2016 Nov 17;128(20):2465-2468.
    *Equal contribution
    – Identification of STAT5b mutations as a typical feature of CD4+ LGL leukemia.
  8. Andersson E, Kuusanmäki H, Bortoluzzi S, Lagström S, Parsons A, Rajala H, van Adrichem A, Eldfors S, Olson T, Clemente MJ, Laasonen A, Ellonen P, Heckman C, Loughran TP, Maciejewski JP, Mustjoki S. Activating somatic mutations outside the SH2-domain of STAT3 in LGL leukemia. Leukemia. 2016 May;30(5):1204-8.
    – Identification of novel activating somatic mutations in STAT3 in LGL leukemia.
  9. Haapaniemi EM, Kaustio M, Rajala HL, van Adrichem AJ, Kainulainen L, Glumoff V, Doffinger R, Kuusanmaki H, Heiskanen-Kosma T, Trotta L, Chiang S, Kulmala P, Eldfors S, Katainen R, Siitonen S, Karjalainen-Lindsberg ML, Kovanen PE, Otonkoski T, Porkka K, Heiskanen K, Hanninen A, Bryceson YT, Uusitalo-Seppala R, Saarela J, Seppanen M, Mustjoki S, Kere J. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3. Blood. 125, 639-648, 2015.
    – Discovery of clonal LGL expansion as an off-target effect of targeted leukemia therapy.
  10. 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.
  11. Jerez A, Clemente MJ, Makishima H, Rajala H, Gomez-Segui I, Olson T, McGraw K, Przychodzen B, Kulasekararaj A, Afable M, Husseinzadeh HD, Hosono N, LeBlanc F, Lagstrom S, Zhang D, Ellonen P, Tichelli A, Nissen C, Lichtin AE, Wodnar-Filipowicz A, Mufti GJ, List AF, Mustjoki S, Loughran TP, Jr., Maciejewski JP. STAT3-mutations indicate the presence of subclinical T cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients. Blood. 2013 Oct 3;122(14):2453-9.
    – Discovery of somatic mutations in patients with AA and MDS.
  12. 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.
  13. 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
  1. 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.
  2. Adnan-Awad S, Kim D, Hohtari H, Javarappa KK, Brandstoetter T, Mayer I, Potdar S, Heckman CA, Kytölä S, Porkka K, Doma E, Sexl V, Kankainen M, Mustjoki S. Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets. Leukemia. 2021 Jul;35(7):1964-1975.
  3. Adnan Awad S, Dufva O, Ianevski, A, Ghimire B, Koski J, Maliniemi P, Thomson D, Schreiber A, Heckman CA, Koskenvesa P, Korhonen M, Porkka K, Branford S, Aittokallio T, Kankainen M, Mustjoki S. RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses. Leukemia 2021;35:1087–1099.
  4. Brück OE, Lallukka-Brück SE, Hohtari HR, Ianevski A, Ebeling FT, Kovanen PE, Kytölä SI, Aittokallio TA, Ramos PM, Porkka KV, Mustjoki SM. Machine Learning of Bone Marrow Histopathology Identifies Genetic and Clinical Determinants in Patients with MDS. Blood Cancer Discov. 2021 Mar 22;2(3):238-249
    - Morphologic features found in the bone marrow of MDS and MDS/MPN patients are associated with genetic and cytogenetic alterations, prognosis and patient demographics.
  5. Dufva O, Kankainen M, Kelkka T, Sekiguchi N, Awad SA, Eldfors S, Yadav B, Kuusanmäki H, Malani D, Andersson EI, Pietarinen P, Saikko L, Kovanen PE, Ojala T, Lee DA, Loughran TP Jr, Nakazawa H, Suzumiya J, Suzuki R, Ko YH, Kim WS, Chuang SS, Aittokallio T, Chan WC, Ohshima K, Ishida F, Mustjoki S. Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target. Nat Commun. 2018 Apr 19;9(1):1567.
    – JAK-STAT signaling importantly contributes to the pathogenesis of the extremely aggressive natural killer cell leukemia.
  6. 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.
  7. Pietarinen PO, Pemovska T, Kontro M, Yadav B, Mpindi JP, Andersson EI, Majumder MM, Kuusanmäki H, Koskenvesa P, Kallioniemi O, Wennerberg K, Heckman CA, Mustjoki S*, Porkka K*. Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing. Blood Cancer J. 2015 May 1;5:e309.
    *Equal contribution
    – Application of high through-put drug sensitivity and resistance testing on blast crisis CML.
  8. Pemovska T, Johnson E, Kontro M, Repasky GA, Chen J, Wells P, Cronin CN, McTigue M, Kallioniemi O, Porkka K*, Murray BW*, Wennerberg K*. Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation. Nature. 2015 Mar 5;519(7541):102-5.
    *Equal contribution
    – Nover drug for T315I mutated BCR-ABL positive leukemia.
  9. Pemovska T*, Kontro M*, Yadav B, Edgren H, Eldfors S, Bespalov M, Ellonen P, Elonen E, Karjalainen R, Kulesskiy E, Lehto A, Lundán T, Majumder M.M, Mattila P, Murumägi A, Mustjoki S, Parsons A, Pirttinen T, Rämet M.E, Turunen L, Knowles J, Aittokallio T*, Heckman C*, Porkka K*, Kallioniemi O*, Wennerberg K*. Individualized Systems Medicine (ISM) strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov. 2013 Dec;3(12):1416-29.
    *Equal contribution
    – Individualized systems medicine for AML.
Related to clinical studies
  1. Kasanen H, Hernberg M, Makela S, Bruck O, Juteau S, Kohtamaki L, Ilander M, Mustjoki S, Kreutzman A. Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients. Cancer immunology, immunotherapy: CII. 2020;69(5):717-30.
  2. Kreutzman A, Yadav B, Brummendorf TH, Gjertsen BT, Hee Lee M, Janssen J, Kasanen T, Koskenvesa P, Lotfi K, Markevärn B, Olsson-Strömberg U, Stentoft J, Stenke L, Söderlund S, Udby L, Richter J, Hjorth-Hansen H, Mustjoki S. Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line. OncoImmunology. 2019;8(9):e1638210.
  3. Ilander M, Olsson-Stromberg U, Schlums H, Guilhot J, Bruck O, Lahteenmaki H, Kasanen T, Koskenvesa P, Soderlund S, Hoglund M, Markevarn B, Sjalander A, Lotfi K, Dreimane A, Lubking A, Holm E, Bjoreman M, Lehmann S, Stenke L, Ohm L, Gedde-Dahl T, Majeed W, Ehrencrona H, Koskela S, Saussele S, Mahon FX, Porkka K, Hjorth-Hansen H, Bryceson YT, Richter J, Mustjoki S. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia. Leukemia. 2017;31(5):1108-1116.
    – Discovery of immunological biomarker for successful therapy discontinuation in leukemia patients. Pan-European collaboration in clinical trial.
  4. Sopper S, Mustjoki S, White D, Hughes T, Valent P, Burchert A, Gjertsen BT, Gastl G, Baldauf M, Trajanoski Z, Giles F, Hochhaus A, Ernst T, Schenk T, Janssen JJ, Ossenkoppele GJ, Porkka K, Wolf D. Reduced CD62L expression on T cells and increased soluble CD62L levels predict molecular response to tyrosine kinase inhibitor (TKI) therapy in early Chronic Phase Chronic Myelogenous Leukemia (CML-CP). J Clin Oncol. 2017;35(2):175-184.
    – Characterization of immunological changes during targeted kinase inhibitor therapy and their correlation with therapy response. Pan-European collaboration in clinical trial.
  5. Thielen N, Richter J, Baldauf M, Barbany G, Fioretos T, Giles F, Gjertsen BT, Hochhaus A, Schuurhuis GJ, Sopper S, Stenke L, Thunberg S, Wolf D, Ossenkoppele G, Porkka K, Janssen J, Mustjoki S. Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy. Clin Cancer Res. 2016;22(16):4030-8.
    – Clinical study in CML first-line treatment, which had the experimental analysis of leukemia stem cells as a primary study end-point.
  6. Mustjoki S, Richter J, Barbany G, Ehrencrona H, Fioretos T, Gedde-Dahl T, Gjertsen BT, Hovland R, Hernesniemi S, Josefsen D, Koskenvesa P, Dybedal I, Markevarn B, Olofsson T, Olsson-Stromberg U, Rapakko K, Thunberg S, Stenke L, Simonsson B, Porkka K, Hjorth-Hansen H. Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients. Leukemia. 2013 Jul;27(7):1520-6.
    – In chronic myeloid leukemia, stem cell count at diagnosis help to predict response to tyrosine kinase inhibitor treatment.