Minna Suvela
University of Helsinki
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Publication
Featured researches published by Minna Suvela.
Blood | 2017
Riikka Karjalainen; Tea Pemovska; Mihaela Popa; Minxia Liu; Komal K. Javarappa; Muntasir Mamun Majumder; Bhagwan Yadav; David Tamborero; Jing Tang; Dmitrii Bychkov; Mika Kontro; Alun Parsons; Minna Suvela; Mireia Mayoral Safont; Kimmo Porkka; Tero Aittokallio; Olli Kallioniemi; Emmet McCormack; Bjørn Tore Gjertsen; Krister Wennerberg; Jonathan Knowles; Caroline Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be a result of the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the effect of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions. In the stroma-based conditions, the AML patient cells exhibited significantly reduced sensitivity to 12% of the tested compounds, including topoisomerase II, B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2), and many tyrosine kinase inhibitors (TKIs). The loss of TKI sensitivity was most pronounced in patient samples harboring FLT3 or PDGFRB alterations. In contrast, the stroma-derived conditions enhanced sensitivity to Janus kinase (JAK) inhibitors. Increased cell viability and resistance to specific drug classes in the BM stroma-derived conditions was a result of activation of alternative signaling pathways mediated by factors secreted by BM stromal cells and involved a switch from BCL2 to BCLXL-dependent cell survival. Moreover, the JAK1/2 inhibitor ruxolitinib restored sensitivity to the BCL2 inhibitor venetoclax in AML patient cells ex vivo in different model systems and in vivo in an AML xenograft mouse model. These findings highlight the potential of JAK inhibitors to counteract stroma-induced resistance to BCL2 inhibitors in AML.
Oncotarget | 2017
Muntasir Mamun Majumder; Raija Silvennoinen; Pekka Anttila; David Tamborero; Samuli Eldfors; Bhagwan Yadav; Riikka Karjalainen; Heikki Kuusanmäki; Juha Lievonen; Alun Parsons; Minna Suvela; Esa Jantunen; Kimmo Porkka; Caroline Heckman
Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.
Cancer Discovery | 2013
Tea Pemovska; Mika Kontro; Bhagwan Yadav; Henrik Edgren; Samuli Eldfors; Agnieszka Szwajda; Henrikki Almusa; Maxim M. Bespalov; Pekka Ellonen; Erkki Elonen; Bjørn Tore Gjertsen; Riikka Karjalainen; Evgeny Kulesskiy; Sonja Lagström; Anna Lehto; Maija Lepistö; Tuija Lundán; Muntasir Mamun Majumder; Jesus M. Lopez Marti; Pirkko Mattila; Astrid Murumägi; Satu Mustjoki; Aino Palva; Alun Parsons; Tero Pirttinen; Maria Rämet; Minna Suvela; Laura Turunen; Imre Västrik; Maija Wolf
Blood | 2012
Caroline Heckman; Mika Kontro; Tea Pemovska; Samuli Eldfors; Henrik Edgren; Evgeny Kulesskiy; Muntasir Mamun Majumder; Riikka Karjalainen; Bhagwan Yadav; Agnieszka Szwajda; Naga Poojitha Kota Venkata; Astrid Murumägi; Disha Malani; Alun Parsons; Petteri Hintsanen; Henrikki Almusa; Jesus M. Lopez Marti; Pekka Ellonen; Pirkko Mattila; Maija Lepistö; Sonja Lagström; Minna Suvela; Satu Mustjoki; Janna Saarela; Tero Aittokallio; Olli Kallioniemi; Krister Wennerberg; Kimmo Porkka
Clinical Lymphoma, Myeloma & Leukemia | 2017
Muntasir Mamun Majumder; David Tamborero; Pekka Anttila; Raija Silvennoinen; Juha Lievonen; Samuli Eldfors; Ashwini Kumar; Alun Parsons; Minna Suvela; Esa Jantunen; Kimmo Porkka; Caroline Heckman
Blood | 2016
Muntasir Mamun Majumder; David Tamborero; Pekka Anttila; Raija Silvennoinen; Samuli Eldfors; Ashwini Kumar; Juha Lievonen; Alun Parsons; Minna Suvela; Esa Jantunen; Kimmo Porkka; Caroline Heckman
Clinical Lymphoma, Myeloma & Leukemia | 2015
Muntasir Mamun Majumder; Raija Silvennoinen; Pekka Anttila; D. Tamborero; Samuli Eldfors; Riikka Karjalainen; Heikki Kuusanmäki; J. Lievonen; Alun Parsons; Minna Suvela; Kimmo Porkka; Caroline Heckman
Clinical Lymphoma, Myeloma & Leukemia | 2015
Riikka Karjalainen; Tea Pemovska; Muntasir Mamun Majumder; Bhagwan Yadav; David Tamborero; Jing Tang; Dmitrii Bychkov; Mika Kontro; Bjørn Tore Gjertsen; Alun Parsons; Minna Suvela; Imre Västrik; Kimmo Porkka; Tero Aittokallio; Olli Kallioniemi; Krister Wennerberg; Jonathan Knowles; Caroline Heckman
Blood | 2015
Muntasir Mamun Majumder; Raija Silvennoinen; Pekka Anttila; David Tamborero; Samuli Eldfors; Juha Lievonen; Riikka Karjalainen; Heikki Kuusanmäki; Alun Parsons; Minna Suvela; Kimmo Porkka; Caroline Heckman
Blood | 2014
David Tamborero; Muntasir Mamun Majumder; Raija Silvennoinen; Samuli Eldfors; Pekka Anttila; Juha Lievonen; Alun Parsons; Minna Suvela; Marjanna Säily; Kimmo Porkka; Caroline Heckman