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25 results on '"ten Hacken, Elisa"'

1. T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia

Author

Roessner, Philipp M., Seufert, Isabelle, Chapaprieta, Vicente, Jayabalan, Ruparoshni, Briesch, Hannah, Massoni-Badosa, Ramon, Boskovic, Pavle, Benckendorff, Julian, Roider, Tobias, Arseni, Lavinia, Coelho, Mariana, Chakraborty, Supriya, Vaca, Alicia M., Sivina, Mariela, Muckenhuber, Markus, Rodriguez-Rodriguez, Sonia, Bonato, Alice, Herbst, Sophie A., Zapatka, Marc, Sun, Clare, Kretzmer, Helene, Naake, Thomas, Bruch, Peter-Martin, Czernilofsky, Felix, ten Hacken, Elisa, Schneider, Martin, Helm, Dominic, Yosifov, Deyan Y., Kauer, Joseph, Danilov, Alexey V., Bewarder, Moritz, Heyne, Kristina, Schneider, Christof, Stilgenbauer, Stephan, Wiestner, Adrian, Mallm, Jan-Philipp, Burger, Jan A., Efremov, Dimitar G., Lichter, Peter, Dietrich, Sascha, Martin-Subero, José I., Rippe, Karsten, and Seiffert, Martina

Published
2024
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2. Activation of Notch and Myc signaling via B cell-restricted depletion of Dnmt3a generates a consistent murine model of chronic lymphocytic leukemia

Author

Biran, Anat, Yin, Shanye, Kretzmer, Helene, Ten Hacken, Elisa, Parvin, Salma, Lucas, Fabienne, Uduman, Mohamed, Gutierrez, Catherine, Dangle, Nathan, Billington, Leah, Regis, Fara Faye, Rassenti, Laura Z, Mohammad, Arman, Hoffmann, Gabriela Brunsting, Stevenson, Kristen, Zheng, Mei, Witten, Elizabeth, Fernandes, Stacey M, Tausch, Eugen, Sun, Clare, Stilgenbauer, Stephan, Brown, Jennifer R, Kipps, Thomas J, Aster, John C, Gnirke, Andreas, Neuberg, Donna S, Letai, Anthony, Wang, Lili, Carrasco, Ruben D, Meissner, Alexander, and Wu, Catherine J

Subjects
Genetics, Lymphoma, Cancer, Rare Diseases, Hematology, Aetiology, 2.1 Biological and endogenous factors, Animals, Anti-Bacterial Agents, Apoptosis, Biomarkers, Tumor, Cell Proliferation, DNA Methyltransferase 3A, Daptomycin, Disease Models, Animal, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Mice, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Prognosis, Proto-Oncogene Proteins c-myc, RNA-Seq, Receptors, Notch, Survival Rate, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous Dnmt3a depletion yields a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haploinsufficient tumor suppressor. B1a cells were confirmed as the cell of origin of disease in this model, and Dnmt3a depletion resulted in focal hypomethylation and activation of Notch and Myc signaling. Amplification of chromosome 15 containing the Myc gene was detected in all CLL mice tested, and infiltration of high-Myc-expressing CLL cells in the spleen was observed. Notably, hyperactivation of Notch and Myc signaling was exclusively observed in the Dnmt3a CLL mice, but not in three other CLL mouse models tested (Sf3b1-Atm, Ikzf3, and MDR), and Dnmt3a-depleted CLL were sensitive to pharmacologic inhibition of Notch signaling in vitro and in vivo. Consistent with these findings, human CLL samples with lower DNMT3A expression were more sensitive to Notch inhibition than those with higher DNMT3A expression. Altogether, these results suggest that Dnmt3a depletion induces CLL that is highly dependent on activation of Notch and Myc signaling. SIGNIFICANCE: Loss of DNMT3A expression is a driving event in CLL and is associated with aggressive disease, activation of Notch and Myc signaling, and enhanced sensitivity to Notch inhibition.

Published
2021

5. Data from In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities

Author

ten Hacken, Elisa, primary, Sewastianik, Tomasz, primary, Yin, Shanye, primary, Hoffmann, Gabriela Brunsting, primary, Gruber, Michaela, primary, Clement, Kendell, primary, Penter, Livius, primary, Redd, Robert A., primary, Ruthen, Neil, primary, Hergalant, Sébastien, primary, Sholokhova, Alanna, primary, Fell, Geoffrey, primary, Parry, Erin M., primary, Broséus, Julien, primary, Guieze, Romain, primary, Lucas, Fabienne, primary, Hernández-Sánchez, María, primary, Baranowski, Kaitlyn, primary, Southard, Jackson, primary, Joyal, Heather, primary, Billington, Leah, primary, Regis, Fara Faye D., primary, Witten, Elizabeth, primary, Uduman, Mohamed, primary, Knisbacher, Binyamin A., primary, Li, Shuqiang, primary, Lyu, Haoxiang, primary, Vaisitti, Tiziana, primary, Deaglio, Silvia, primary, Inghirami, Giorgio, primary, Feugier, Pierre, primary, Stilgenbauer, Stephan, primary, Tausch, Eugen, primary, Davids, Matthew S., primary, Getz, Gad, primary, Livak, Kenneth J., primary, Bozic, Ivana, primary, Neuberg, Donna S., primary, Carrasco, Ruben D., primary, and Wu, Catherine J., primary

Published
2023
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6. Supplementary Tables and Figures from SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

Author

Yigit, Burcu, primary, Wang, Ninghai, primary, ten Hacken, Elisa, primary, Chen, Shih-Shih, primary, Bhan, Atul K., primary, Suarez-Fueyo, Abel, primary, Katsuyama, Eri, primary, Tsokos, George C., primary, Chiorazzi, Nicholas, primary, Wu, Catherine J., primary, Burger, Jan A., primary, Herzog, Roland W., primary, Engel, Pablo, primary, and Terhorst, Cox, primary

Published
2023
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7. Data from SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

Author

Yigit, Burcu, primary, Wang, Ninghai, primary, ten Hacken, Elisa, primary, Chen, Shih-Shih, primary, Bhan, Atul K., primary, Suarez-Fueyo, Abel, primary, Katsuyama, Eri, primary, Tsokos, George C., primary, Chiorazzi, Nicholas, primary, Wu, Catherine J., primary, Burger, Jan A., primary, Herzog, Roland W., primary, Engel, Pablo, primary, and Terhorst, Cox, primary

Published
2023
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8. Supplementary Legends from SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

Author

Yigit, Burcu, primary, Wang, Ninghai, primary, ten Hacken, Elisa, primary, Chen, Shih-Shih, primary, Bhan, Atul K., primary, Suarez-Fueyo, Abel, primary, Katsuyama, Eri, primary, Tsokos, George C., primary, Chiorazzi, Nicholas, primary, Wu, Catherine J., primary, Burger, Jan A., primary, Herzog, Roland W., primary, Engel, Pablo, primary, and Terhorst, Cox, primary

Published
2023
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9. Supplementary Figures from In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities

Author

ten Hacken, Elisa, primary, Sewastianik, Tomasz, primary, Yin, Shanye, primary, Hoffmann, Gabriela Brunsting, primary, Gruber, Michaela, primary, Clement, Kendell, primary, Penter, Livius, primary, Redd, Robert A., primary, Ruthen, Neil, primary, Hergalant, Sébastien, primary, Sholokhova, Alanna, primary, Fell, Geoffrey, primary, Parry, Erin M., primary, Broséus, Julien, primary, Guieze, Romain, primary, Lucas, Fabienne, primary, Hernández-Sánchez, María, primary, Baranowski, Kaitlyn, primary, Southard, Jackson, primary, Joyal, Heather, primary, Billington, Leah, primary, Regis, Fara Faye D., primary, Witten, Elizabeth, primary, Uduman, Mohamed, primary, Knisbacher, Binyamin A., primary, Li, Shuqiang, primary, Lyu, Haoxiang, primary, Vaisitti, Tiziana, primary, Deaglio, Silvia, primary, Inghirami, Giorgio, primary, Feugier, Pierre, primary, Stilgenbauer, Stephan, primary, Tausch, Eugen, primary, Davids, Matthew S., primary, Getz, Gad, primary, Livak, Kenneth J., primary, Bozic, Ivana, primary, Neuberg, Donna S., primary, Carrasco, Ruben D., primary, and Wu, Catherine J., primary

Published
2023
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10. Supplementary Tables from In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities

Author

ten Hacken, Elisa, primary, Sewastianik, Tomasz, primary, Yin, Shanye, primary, Hoffmann, Gabriela Brunsting, primary, Gruber, Michaela, primary, Clement, Kendell, primary, Penter, Livius, primary, Redd, Robert A., primary, Ruthen, Neil, primary, Hergalant, Sébastien, primary, Sholokhova, Alanna, primary, Fell, Geoffrey, primary, Parry, Erin M., primary, Broséus, Julien, primary, Guieze, Romain, primary, Lucas, Fabienne, primary, Hernández-Sánchez, María, primary, Baranowski, Kaitlyn, primary, Southard, Jackson, primary, Joyal, Heather, primary, Billington, Leah, primary, Regis, Fara Faye D., primary, Witten, Elizabeth, primary, Uduman, Mohamed, primary, Knisbacher, Binyamin A., primary, Li, Shuqiang, primary, Lyu, Haoxiang, primary, Vaisitti, Tiziana, primary, Deaglio, Silvia, primary, Inghirami, Giorgio, primary, Feugier, Pierre, primary, Stilgenbauer, Stephan, primary, Tausch, Eugen, primary, Davids, Matthew S., primary, Getz, Gad, primary, Livak, Kenneth J., primary, Bozic, Ivana, primary, Neuberg, Donna S., primary, Carrasco, Ruben D., primary, and Wu, Catherine J., primary

Published
2023
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12. Supplementary Tables 1,2,3,4 from Ofatumumab and Lenalidomide for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia: Correlation between Responses and Immune Characteristics

Author

Vitale, Candida, primary, Falchi, Lorenzo, primary, ten Hacken, Elisa, primary, Gao, Hui, primary, Shaim, Hila, primary, Van Roosbroeck, Katrien, primary, Calin, George, primary, O'Brien, Susan, primary, Faderl, Stefan, primary, Wang, Xuemei, primary, Wierda, William G., primary, Rezvani, Katayoun, primary, Reuben, James M., primary, Burger, Jan A., primary, Keating, Michael J., primary, and Ferrajoli, Alessandra, primary

Published
2023
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13. Supplementary Figures 1,2,3,4,5 from Ofatumumab and Lenalidomide for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia: Correlation between Responses and Immune Characteristics

Author

Vitale, Candida, primary, Falchi, Lorenzo, primary, ten Hacken, Elisa, primary, Gao, Hui, primary, Shaim, Hila, primary, Van Roosbroeck, Katrien, primary, Calin, George, primary, O'Brien, Susan, primary, Faderl, Stefan, primary, Wang, Xuemei, primary, Wierda, William G., primary, Rezvani, Katayoun, primary, Reuben, James M., primary, Burger, Jan A., primary, Keating, Michael J., primary, and Ferrajoli, Alessandra, primary

Published
2023
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14. Supplementary Data from Activation of Notch and Myc Signaling via B-cell–Restricted Depletion of Dnmt3a Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia

Author

Biran, Anat, primary, Yin, Shanye, primary, Kretzmer, Helene, primary, ten Hacken, Elisa, primary, Parvin, Salma, primary, Lucas, Fabienne, primary, Uduman, Mohamed, primary, Gutierrez, Catherine, primary, Dangle, Nathan, primary, Billington, Leah, primary, Regis, Fara Faye, primary, Rassenti, Laura Z., primary, Mohammad, Arman, primary, Hoffmann, Gabriela Brunsting, primary, Stevenson, Kristen, primary, Zheng, Mei, primary, Witten, Elizabeth, primary, Fernandes, Stacey M., primary, Tausch, Eugen, primary, Sun, Clare, primary, Stilgenbauer, Stephan, primary, Brown, Jennifer R., primary, Kipps, Thomas J., primary, Aster, John C., primary, Gnirke, Andreas, primary, Neuberg, Donna S., primary, Letai, Anthony, primary, Wang, Lili, primary, Carrasco, Ruben D., primary, Meissner, Alexander, primary, and Wu, Catherine J., primary

Published
2023
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15. Data from Activation of Notch and Myc Signaling via B-cell–Restricted Depletion of Dnmt3a Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia

Author

Biran, Anat, primary, Yin, Shanye, primary, Kretzmer, Helene, primary, ten Hacken, Elisa, primary, Parvin, Salma, primary, Lucas, Fabienne, primary, Uduman, Mohamed, primary, Gutierrez, Catherine, primary, Dangle, Nathan, primary, Billington, Leah, primary, Regis, Fara Faye, primary, Rassenti, Laura Z., primary, Mohammad, Arman, primary, Hoffmann, Gabriela Brunsting, primary, Stevenson, Kristen, primary, Zheng, Mei, primary, Witten, Elizabeth, primary, Fernandes, Stacey M., primary, Tausch, Eugen, primary, Sun, Clare, primary, Stilgenbauer, Stephan, primary, Brown, Jennifer R., primary, Kipps, Thomas J., primary, Aster, John C., primary, Gnirke, Andreas, primary, Neuberg, Donna S., primary, Letai, Anthony, primary, Wang, Lili, primary, Carrasco, Ruben D., primary, Meissner, Alexander, primary, and Wu, Catherine J., primary

Published
2023
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17. In VivoModeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities

Author

ten Hacken, Elisa, primary, Sewastianik, Tomasz, additional, Yin, Shanye, additional, Hoffmann, Gabriela Brunsting, additional, Gruber, Michaela, additional, Clement, Kendell, additional, Penter, Livius, additional, Redd, Robert A., additional, Ruthen, Neil, additional, Hergalant, Sébastien, additional, Sholokhova, Alanna, additional, Fell, Geoffrey, additional, Parry, Erin M., additional, Broséus, Julien, additional, Guieze, Romain, additional, Lucas, Fabienne, additional, Hernández-Sánchez, María, additional, Baranowski, Kaitlyn, additional, Southard, Jackson, additional, Joyal, Heather, additional, Billington, Leah, additional, Regis, Fara Faye D., additional, Witten, Elizabeth, additional, Uduman, Mohamed, additional, Knisbacher, Binyamin A., additional, Li, Shuqiang, additional, Lyu, Haoxiang, additional, Vaisitti, Tiziana, additional, Deaglio, Silvia, additional, Inghirami, Giorgio, additional, Feugier, Pierre, additional, Stilgenbauer, Stephan, additional, Tausch, Eugen, additional, Davids, Matthew S., additional, Getz, Gad, additional, Livak, Kenneth J., additional, Bozic, Ivana, additional, Neuberg, Donna S., additional, Carrasco, Ruben D., additional, and Wu, Catherine J., additional

Published
2022
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23. Loss-of-function lesions impact B-cell development and fitness but are insufficient to drive CLL in mouse models.

Author

ten Hacken E, Yin S, Redd R, Hernández Sánchez M, Clement K, Hoffmann GB, Regis FF, Witten E, Li S, Neuberg D, Pinello L, Livak KJ, and Wu CJ

Subjects
Mice, Animals, B-Lymphocytes pathology, Receptors, Antigen, B-Cell, Hematopoiesis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell pathology
Published
2023
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24. Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models.

Author

Penter L, Ten Hacken E, Southard J, Lareau CA, Ludwig LS, Li S, Neuberg DS, Livak KJ, and Wu CJ

Subjects
Animals, Mice, Mitochondria genetics, Chromatin, Mutation, DNA, Mitochondrial genetics, Neoplasms genetics
Abstract

Murine models are indispensable tools for functional genomic studies and preclinical testing of novel therapeutic approaches. Mitochondrial single-cell assay for transposase-accessible chromatin using sequencing (mtscATAC-seq) enables the dissection of cellular heterogeneity and clonal dynamics by capturing chromatin accessibility, copy-number variations (CNV), and mitochondrial DNA (mtDNA) mutations, yet its applicability to murine studies remains unexplored. By leveraging mtscATAC-seq in novel chronic lymphocytic leukemia and Richter syndrome mouse models, we report the detection of mtDNA mutations, particularly in highly proliferative murine cells, alongside CNV and chromatin state changes indicative of clonal evolution upon secondary transplant. This study thus demonstrates the feasibility and utility of multi-modal single-cell and natural barcoding approaches to characterize murine cancer models., Significance: mtDNA mutations can serve as natural barcodes to enable lineage tracing in murine cancer models, which can be used to provide new insights into disease biology and to identify therapeutic vulnerabilities., (©2022 American Association for Cancer Research.)

Published
2023
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25. In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities.

Author

Ten Hacken E, Sewastianik T, Yin S, Hoffmann GB, Gruber M, Clement K, Penter L, Redd RA, Ruthen N, Hergalant S, Sholokhova A, Fell G, Parry EM, Broséus J, Guieze R, Lucas F, Hernández-Sánchez M, Baranowski K, Southard J, Joyal H, Billington L, Regis FFD, Witten E, Uduman M, Knisbacher BA, Li S, Lyu H, Vaisitti T, Deaglio S, Inghirami G, Feugier P, Stilgenbauer S, Tausch E, Davids MS, Getz G, Livak KJ, Bozic I, Neuberg DS, Carrasco RD, and Wu CJ

Subjects
Humans, Animals, Mice, Phosphatidylinositol 3-Kinases genetics, B-Lymphocytes, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Non-Hodgkin
Abstract

Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e., Richter syndrome (RS)]. Evolutionary trajectories of 64 mice carrying diverse combinatorial gene assortments revealed coselection of mutations in Trp53, Mga, and Chd2 and the dual impact of clonal Mga/Chd2 mutations on E2F/MYC and interferon signaling dysregulation. Comparative human and murine RS analyses demonstrated tonic PI3K signaling as a key feature of transformed disease, with constitutive activation of the AKT and S6 kinases, downmodulation of the PTEN phosphatase, and convergent activation of MYC/PI3K transcriptional programs underlying enhanced sensitivity to MYC/mTOR/PI3K inhibition. This robust experimental system presents a unique framework to study lymphoid biology and therapy., Significance: Mouse models reflective of the genetic complexity and heterogeneity of human tumors remain few, including those able to recapitulate transformation to aggressive disease histologies. Herein, we model CLL transformation into RS through multiplexed in vivo gene editing, providing key insight into the pathophysiology and therapeutic vulnerabilities of transformed disease. This article is highlighted in the In This Issue feature, p. 101., (© 2022 American Association for Cancer Research.)

Published
2023
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