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12 results on '"Cecilia Reyneri"'

1. P408: COMBINATORIAL BCL-2 FAMILY EXPRESSION IN ACUTE MYELOID LEUKEMIA STEM CELLS PREDICTS CLINICAL RESPONSE TO AZACITIDINE/VENETOCLAX

Author

Simon Renders, Alexander Waclawiczek, Aino-Maija Leppä, Karolin Stumpf, Barbara Betz, Cecilia Reyneri, Elisa Donato, Maike Janssen, Julia Unglaub, Rabia Shahswar, Simon Raffel, Michael Hundemer, Michael Heuser, Carsten Müller-Tidow, Tim Sauer, and Andreas Trumpp

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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2. Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Alexander Waclawiczek, Aino-Maija Leppä, Simon Renders, Karolin Stumpf, Cecilia Reyneri, Barbara Betz, Maike Janssen, Rabia Shahswar, Elisa Donato, Darja Karpova, Vera Thiel, Julia M. Unglaub, Susanna Grabowski, Stefanie Gryzik, Lisa Vierbaum, Richard F. Schlenk, Christoph Röllig, Michael Hundemer, Caroline Pabst, Michael Heuser, Simon Raffel, Carsten Müller-Tidow, Tim Sauer, and Andreas Trumpp

Subjects
Oncology
Abstract

The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based “Mediators of apoptosis combinatorial score” (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN. Significance: Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making.

Published
2023

3. Supplementary Figure 2 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Transcriptomic and functional characterization of LSC-like cells

Published
2023

4. Supplementary Figure 1 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Cell line sensitivity and additional patient data

Published
2023

5. SupplementaryFigure 6 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Comparison of MAC-Score and BH-3 profiling based response prediction

Published
2023

6. Supplementary Figure 7 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

MAC-Score predict response within mutational subgroups

Published
2023

7. Data from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based “Mediators of apoptosis combinatorial score” (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN.Significance:Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making.

Published
2023

8. Supplementary Figure 5 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Subpopulation specific Bcl-2 family levels and time on HMA/Venetoclax

Published
2023

9. Supplementary Figure 4 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Subpopulation specific Bcl-2 family levels and response to HMA/Venetoclax

Published
2023

10. Supplementary Figure 3 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

Bcl-2 family gene expression in LSCs predicts in vitro response to HMA/VEN

Published
2023

11. Supplementary Tables 1-7 from Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax

Author

Andreas Trumpp, Tim Sauer, Carsten Müller-Tidow, Simon Raffel, Michael Heuser, Caroline Pabst, Michael Hundemer, Christoph Röllig, Richard F. Schlenk, Lisa Vierbaum, Stefanie Gryzik, Susanna Grabowski, Julia M. Unglaub, Vera Thiel, Darja Karpova, Elisa Donato, Rabia Shahswar, Maike Janssen, Barbara Betz, Cecilia Reyneri, Karolin Stumpf, Simon Renders, Aino-Maija Leppä, and Alexander Waclawiczek

Abstract

7 Tables showing: molecular and clinical patient data, cell line info, antibody panels and overview of assays used

Published
2023

12. Macs - a Leukemic Stem Cell- Based Predictor of Clinical Response to Venetoclax and Other BH3 Mimetics for Acute Myeloid Leukemia

Author

Simon Renders, Alexander Waclawiczek, Aino-Maija Leppä, Cecilia Reyneri, Barbara Betz, Karolin Stumpf, Maike Janssen, Julia M. Unglaub, Elisa Donato, Rabia Shahswar, Simon Raffel, Michael Heuser, Richard F. Schlenk, Michael Hundemer, Tim Sauer, Carsten Müller-Tidow, and Andreas Trumpp

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

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