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16 results on '"Kytölä, Sari"'

2. Robust scoring of selective drug responses for patient-tailored therapy selection

Author

Chen, Yingjia, primary, He, Liye, additional, Ianevski, Aleksandr, additional, Ayuda-Durán, Pilar, additional, Potdar, Swapnil, additional, Saarela, Jani, additional, Miettinen, Juho J., additional, Kytölä, Sari, additional, Miettinen, Susanna, additional, Manninen, Mikko, additional, Heckman, Caroline A., additional, Enserink, Jorrit M., additional, Wennerberg, Krister, additional, and Aittokallio, Tero, additional

Published
2023
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3. P409: BCL-2/BCL-XL INHIBITION INDUCES APOPTOSIS AND CIRCUMVENTS VENETOCLAX RESISTANCE IN TP53-MUTATED ACUTE MYELOID LEUKEMIA

Author

Vänttinen, Ida, primary, Kytölä, Sari, additional, Dufva, Olli, additional, Hellesøy, Monica, additional, Gullaksen, Stein-Erik, additional, Ruokoranta, Tanja, additional, Brück, Oscar, additional, Siitonen, Sanna, additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpilainen, Johanna, additional, Siitonen, Timo, additional, Tore Gjertsen, Bjorn, additional, Heckman, Caroline, additional, Kuusanmäki, Heikki, additional, and Kontro, Mika, additional

Published
2023
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4. P562: CAPILLARY BLOOD SAMPLING ALLOWS FEASIBLE METHOD FOR VENETOCLAX CONCENTRATION MEASUREMENT IN AN ACADEMIC MULTICENTER CLINICAL TRIAL CONTEXT

Author

Kytölä, Sari, primary, Vänttinen, Ida, additional, Kuusanmäki, Heikki, additional, Ruokoranta, Tanja, additional, Kurkela, Mika, additional, Kiiski, Johanna, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Ettala, Pia, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, Pyörälä, Marja, additional, T. Backman, Janne, additional, Niemi, Mikko, additional, and Kontro, Mika, additional

Published
2023
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5. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

Author

Kuusanmäki, Heikki, Kytölä, Sari, Vänttinen, Ida, Ruokoranta, Tanja, Ranta, Amanda, Huuhtanen, Jani, Suvela, Minna, Parsons, Alun, Holopainen, Annasofia, Partanen, Anu, Kuusisto, Milla E.L., Koskela, Sirpa, Räty, Riikka, Itälä-Remes, Maija, Västrik, Imre, Dufva, Olli, Siitonen, Sanna, Porkka, Kimmo, Wennerberg, Krister, Heckman, Caroline A., Ettala, Pia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, Kontro, Mika, Kuusanmäki, Heikki, Kytölä, Sari, Vänttinen, Ida, Ruokoranta, Tanja, Ranta, Amanda, Huuhtanen, Jani, Suvela, Minna, Parsons, Alun, Holopainen, Annasofia, Partanen, Anu, Kuusisto, Milla E.L., Koskela, Sirpa, Räty, Riikka, Itälä-Remes, Maija, Västrik, Imre, Dufva, Olli, Siitonen, Sanna, Porkka, Kimmo, Wennerberg, Krister, Heckman, Caroline A., Ettala, Pia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, and Kontro, Mika

Abstract

The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity.

Published
2023

6. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

Author

Kuusanmäki, Heikki, primary, Kytölä, Sari, additional, Vänttinen, Ida, additional, Ruokoranta, Tanja, additional, Ranta, Amanda, additional, Huuhtanen, Jani, additional, Suvela, Minna, additional, Parsons, Alun, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Västrik, Imre, additional, Dufva, Olli, additional, Siitonen, Sanna, additional, Porkka, Kimmo, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, and Kontro, Mika, additional

Published
2022
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7. Ex Vivo Venetoclax Sensitivity Testing Predicts Response and Overall Survival in De Novo and s/R/R AML Patients Treated with Azacitidine and Venetoclax

Author

Kytölä, Sari, primary, Vänttinen, Ida, additional, Ruokoranta, Tanja, additional, Holopainen, Annasofia, additional, Partanen, Anu, additional, Kuusisto, Milla E.L., additional, Koskela, Sirpa, additional, Räty, Riikka, additional, Itälä-Remes, Maija, additional, Ranta, Amanda, additional, Suvela, Minna, additional, Parsons, Alun, additional, Västrik, Imre, additional, Siitonen, Sanna M., additional, Porkka, Kimmo, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, Pyörälä, Marja, additional, Kuusanmäki, Heikki, additional, and Kontro, Mika, additional

Published
2022
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8. Ex Vivo Drug Sensitivity Testing to Predict Response to Venetoclax + Azacitidine in Acute Myeloid Leukemia: Interim Results of the Prospective Multicenter Phase II Venex Trial

Author

Kuusanmäki, Heikki, primary, Kytölä, Sari, additional, Vänttinen, Ida, additional, Ranta, Amanda, additional, Ruokoranta, Tanja, additional, Holopainen, Annasofia, additional, Koskela, Sirpa, additional, Kuusisto, Milla E.L., additional, Porkka, Kimmo, additional, Räty, Riikka, additional, Västrik, Imre, additional, Wennerberg, Krister, additional, Heckman, Caroline A., additional, Ettala, Pia, additional, Pyörälä, Marja, additional, Rimpiläinen, Johanna, additional, Siitonen, Timo, additional, and Kontro, Mika, additional

Published
2021
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9. Abstract 3899: Discovery and clinical implementation of individualized therapies in acute myeloid leukemia based on ex vivo drug sensitivity testing and multi-omics profiling

Author

Malani, Disha, primary, Kumar, Ashwini, additional, Yadav, Bhagwan, additional, Kontro, Mika, additional, Potdar, Swapnil, additional, Brück, Oscar, additional, Kytölä, Sari, additional, Saarela, Jani, additional, Eldfors, Samuli, additional, Ojamies, Poojitha, additional, Riikka, Karjalainen, additional, Majumder, Muntasir Mamun, additional, Västrik, Imre, additional, Ellonen, Pekka, additional, Kankainen, Matti, additional, Suvela, Minna, additional, Knappila, Siv, additional, Parson, Alun, additional, Palva, Aino, additional, Mattila, Pirkko, additional, Kulesskiy1, Evgeny, additional, Turunen, Laura, additional, Laamanen, Karoliina, additional, Lehtinen, Elina, additional, Mikkonen, Piia, additional, Nurmi, Maria, additional, Timonen, Sanna, additional, Murumägi, Astrid, additional, Gjersten, Bjorn Tore, additional, Mustjoki, Satu, additional, Aittokallio, Tero, additional, Wennerberg, Krister, additional, Anders, Simon, additional, Wolf, Maija, additional, Heckman, Caroline, additional, Porkka, Kimmo, additional, and Kallioniemi, Olli, additional

Published
2018
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10. Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial

Author

Kytölä, Sari, Vänttinen, Ida, Ruokoranta, Tanja, Partanen, Anu, Holopainen, Annasofia, Saad, Joseph, Kuusisto, Milla E. L., Koskela, Sirpa, Räty, Riikka, Itälä-Remes, Maija, Västrik, Imre, Suvela, Minna, Parsons, Alun, Porkka, Kimmo, Wennerberg, Krister, Heckman, Caroline A., Jalkanen, Tero, Huttunen, Teppo, Ettala, Pia, Rimpiläinen, Johanna, Siitonen, Timo, Pyörälä, Marja, Kuusanmäki, Heikki, and Kontro, Mika

Abstract

•Blast-specific ex vivo venetoclax sensitivity correlated strongly with treatment responses and predicted longer survival.•VenEx trial showed that ex vivo drug sensitivity is beneficial for selecting patients with R/R or sAML for venetoclax-azacitidine therapy.

Published
2024
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11. Targeting Venetoclax Resistance in TP53-Mutated Acute Myeloid Leukemia

Author

Vänttinen, Ida, Ruokoranta, Tanja, Saad, Joseph J, Kytölä, Sari, Hellesøy, Monica, Gullaksen, Stein-Erik, Ettala, Pia-Sofia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, Wennerberg, Krister, Gjertsen, Bjorn T., Heckman, Caroline A., Kontro, Mika, and Kuusanmäki, Heikki

Abstract

Introduction: The combination therapy of Venetoclax (Ven) and Azacitidine (Aza) has shown remarkable improvements in the treatment of acute myeloid leukemia (AML) patients not eligible for chemotherapy. Nevertheless, patients with TP53-mutated AML are more prone to have a refractory disease or develop rapid resistance. A recent study indicated that a combined expression ratio of BCL-2, BCL-XL and MCL-1 proteins in leukemic stem cells predicts clinical response to Ven+Aza (Waclawiczek et al. 2023). Furthermore, our previous work has demonstrated that erythroid and megakaryoblastic leukemia blasts are more dependent on BCL-XL than BCL-2 (Kuusanmäki et al. 2023). Emerging evidence suggests that the erythroid-biased differentiation and gene signature is enhanced in many TP53-mutated patients (Rodriquez-Meira et al. 2022). Here we hypothesized that in TP53 -mutated AML, leukemic blasts correspond more closely to megakaryocyte-erythroid progenitors (MEPs) leading to an unfavorable BCL-2 family expression ratio, which can be associated with poor responses to Ven. Consequently, we aimed to identify novel compounds targeting this specific patient subgroup.

Published
2023
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13. Ex VivoDrug Sensitivity Testing to Predict Response to Venetoclax + Azacitidine in Acute Myeloid Leukemia: Interim Results of the Prospective Multicenter Phase II Venex Trial

Author

Kuusanmäki, Heikki, Kytölä, Sari, Vänttinen, Ida, Ranta, Amanda, Ruokoranta, Tanja, Holopainen, Annasofia, Koskela, Sirpa, Kuusisto, Milla E.L., Porkka, Kimmo, Räty, Riikka, Västrik, Imre, Wennerberg, Krister, Heckman, Caroline A., Ettala, Pia, Pyörälä, Marja, Rimpiläinen, Johanna, Siitonen, Timo, and Kontro, Mika

Abstract

Background

Published
2021
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14. Aspariginase-Triggered Hyperglycerimedia: An Analysis on Germline Regulatory Gene Variations in Adult Acute Lymphoblastic Leukemia Patients

Author

Kytölä, Sari, Rantamo, Suvi, Jauhiainen, Matti, Porkka, Kimmo, Kilpivaara, Outi, and Wartiovaara-Kautto, Ulla

Abstract

Asparaginase (ASP) is considered as a backbone of successful treatment of acute lymphoblastic leukemia (ALL). Cell growth and division of malignant lymphoblasts are highly dependent on asparagine and glutamine. ASP depletes them from extracellular fluid which leads to apoptosis of lymphoblasts. Aside from the aimed antileukemic properties, asparaginase exposes patients to multiple adverse effects including severe hypertriglyceridemia which potentially hampers efficient leukemia therapy. Molecular background of ASP-induced hypertriglyceridemia and its regulators are not well known. We aimed to investigate constitutional genetic factors as biomarkers for hypertriglyceridemia following ASP therapy.

Published
2017
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15. Ex vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trial.

Author

Kytölä S, Vänttinen I, Ruokoranta T, Partanen A, Holopainen A, Saad J, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Suvela M, Parsons A, Porkka K, Wennerberg K, Heckman CA, Jalkanen T, Huttunen T, Ettala P, Rimpiläinen J, Siitonen T, Pyörälä M, Kuusanmäki H, and Kontro M

Subjects
Humans, Middle Aged, Female, Male, Aged, Adult, Aged, 80 and over, Prospective Studies, Antineoplastic Agents therapeutic use, Young Adult, Treatment Outcome, Remission Induction, Prognosis, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Sulfonamides therapeutic use
Abstract

Abstract: The B-cell lymphoma 2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial. The trial recruited 104 participants with previously untreated (n = 48), R/R (n = 39), or previously treated secondary AML (sAML) (n = 17). The primary end point was complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in ex vivo sensitive trial participants during the first 3 therapy cycles. The key secondary end points included the correlations between ex vivo drug sensitivity, responses, and survival. Venetoclax sensitivity was successfully assessed in 102 of 104 participants, with results available within a median of 3 days from sampling. In previously untreated AML, ex vivo sensitivity corresponded to an 85% (34/40) CR/CRi rate, with a median overall survival (OS) of 28.7 months, compared with 5.5 months for ex vivo resistant patients (P = .002). For R/R/sAML, ex vivo sensitivity resulted in a 62% CR/CRi rate (21/34) and median OS of 9.7 vs 3.3 months for ex vivo resistant patients (P < .001). In univariate and multivariate analysis, ex vivo venetoclax sensitivity was the strongest predictor for a favorable treatment response and survival. This trial demonstrates the feasibility of integrating ex vivo drug testing into clinical practice to identify patients with AML, particularly in the R/R setting, who benefit from venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT04267081., (© 2025 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Published
2025
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16. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia.

Author

Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyörälä M, Rimpiläinen J, Siitonen T, and Kontro M

Subjects
Humans, Prospective Studies, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
Abstract

The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity. This trial is registered with ClinicalTrials.gov identifier: NCT04267081.

Published
2023
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