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144 results on '"Harrington, Bonnie K."'

1. The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling

Author

Marr, Alexander R., Halpin, Madeline, Corbin, Dominique L., Asemelash, Yerdanos, Sher, Steven, Gordon, Britten K., Whipp, Ethan C., Mitchell, Shaneice, Harrington, Bonnie K., Orwick, Shelley, Benrashid, Samon, Goettl, Virginia M., Yildiz, Vedat, Mitchell, Andrew D., Cahn, Olivia, Mims, Alice S., Larkin, Karilyn T. M., Long, Meixao, Blachly, James, Woyach, Jennifer A., Lapalombella, Rosa, and Grieselhuber, Nicole R.

Published
2024
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2. Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation

Author

Hing, Zachary A., Walker, Janek S., Whipp, Ethan C., Brinton, Lindsey, Cannon, Matthew, Zhang, Pu, Sher, Steven, Cempre, Casey B., Brown, Fiona, Smith, Porsha L., Agostinelli, Claudio, Pileri, Stefano A., Skinner, Jordan N., Williams, Katie, Phillips, Hannah, Shaffer, Jami, Beaver, Larry P., Pan, Alexander, Shin, Kyle, Gregory, Charles T., Ozer, Gulcin H., Yilmaz, Selen A., Harrington, Bonnie K., Lehman, Amy M., Yu, Lianbo, Coppola, Vincenzo, Yan, Pearlly, Scherle, Peggy, Wang, Min, Pitis, Philip, Xu, Chaoyi, Vaddi, Kris, Chen-Kiang, Selina, Woyach, Jennifer, Blachly, James S., Alinari, Lapo, Yang, Yiping, Byrd, John C., Baiocchi, Robert A., Blaser, Bradley W., and Lapalombella, Rosa

Published
2023
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4. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease

Author

Dubovsky, Jason A, Flynn, Ryan, Du, Jing, Harrington, Bonnie K, Zhong, Yiming, Kaffenberger, Benjamin, Yang, Carrie, Towns, William H, Lehman, Amy, Johnson, Amy J, Muthusamy, Natarajan, Devine, Steven M, Jaglowski, Samantha, Serody, Jonathan S, Murphy, William J, Munn, David H, Luznik, Leo, Hill, Geoffrey R, Wong, Henry K, MacDonald, Kelli KP, Maillard, Ivan, Koreth, John, Elias, Laurence, Cutler, Corey, Soiffer, Robert J, Antin, Joseph H, Ritz, Jerome, Panoskaltsis-Mortari, Angela, Byrd, John C, and Blazar, Bruce R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Stem Cell Research - Nonembryonic - Non-Human, Hematology, Rare Diseases, Transplantation, Orphan Drug, Regenerative Medicine, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adenine, Animals, Disease-Free Survival, Drug Evaluation, Preclinical, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Immunologic Factors, Lymphocyte Activation, Mice, Inbred C57BL, Piperidines, Pyrazoles, Pyrimidines, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Bruton's tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity. Here, we evaluated whether ibrutinib could reverse established cGVHD in 2 complementary murine models, a model interrogating T cell-driven sclerodermatous cGVHD and an alloantibody-driven multiorgan system cGVHD model that induces bronchiolar obliterans (BO). In the T cell-mediated sclerodermatous cGVHD model, ibrutinib treatment delayed progression, improved survival, and ameliorated clinical and pathological manifestations. In the alloantibody-driven cGVHD model, ibrutinib treatment restored pulmonary function and reduced germinal center reactions and tissue immunoglobulin deposition. Animals lacking BTK and ITK did not develop cGVHD, indicating that these molecules are critical to cGVHD development. Furthermore, ibrutinib treatment reduced activation of T and B cells from patients with active cGVHD. Our data demonstrate that B cells and T cells drive cGVHD and suggest that ibrutinib has potential as a therapeutic agent, warranting consideration for cGVHD clinical trials.

Published
2014

5. PI3K p110[delta] inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression

Author

Dong, Shuai, Harrington, Bonnie K., Hu, Eileen Y., Greene, Joseph T., Lehman, Amy M., Tran, Minh, Wasmuth, Ronni L., Long, Meixiao, Muthusamy, Natarajan, Brown, Jennifer R., Johnson, Amy J., and Byrd, John C.

Subjects
Immune system -- Research, Lymphocytic leukemia -- Development and progression -- Care and treatment, Molecular targeted therapy -- Usage, T cells -- Research, Health care industry
Abstract

Targeted therapy with small molecules directed at essential survival pathways in leukemia represents a major advance, including the phosphatidylinositol-3'-kinase (PI3K) p110[delta] inhibitor idelalisib. Here, we found that genetic inactivation of p110[delta] ([p110[delta].sup.D910A/D910A]) in the E[mu]-TCL1 murine chronic lymphocytic leukemia (CLL) model impaired B cell receptor signaling and B cell migration, and significantly delayed leukemia pathogenesis. Regardless of TCL1 expression, p110[delta] inactivation led to rectal prolapse in mice resembling autoimmune colitis in patients receiving idelalisib. Moreover, we showed that p110[delta] inactivation in the microenvironment protected against CLL and acute myeloid leukemia. After receiving higher numbers of TCL1 leukemia cells, half of [p110[delta].sup.D910A/D910A] mice spontaneously recovered from high disease burden and resisted leukemia rechallenge. Despite disease resistance, [p110[delta].sup.D910A/D910A] mice exhibited compromised CD4+ and [CD8.sup.+] T cell response, and depletion of [CD4.sup.+] or [CD8.sup.+] T cells restored leukemia. Interestingly, [p110[delta].sup.D910A/D910A] mice showed significantly impaired Treg expansion that associated with disease clearance. Reconstitution of [p110[delta].sup.D910A/D910A] mice with [p110[delta].sup.WT/WT] Tregs reversed leukemia resistance. Our findings suggest that p110[delta] inhibitors may have direct antileukemic and indirect immune- activating effects, further supporting that p110[delta] blockade may have a broader immune-modulatory role in types of leukemia that are not sensitive to p110[delta] inhibition., IntroductionThe development of chronic lymphocytic leukemia (CLL) is the consequence of malignant cell transformation, microenvironment-induced proliferation, and evasion of immune surveillance (1-3). Overwhelming evidence has highlighted the critical role that [...]

Published
2019
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6. Data from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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7. Suppl Table 2 from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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8. Suppl Figure 1 from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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9. Supplemental Methods from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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10. Suppl Table 1 from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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11. Suppl Figure 2 from The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, primary, Smith, Lisa L., primary, Greene, J.T., primary, Muhowski, Elizabeth M., primary, Fabian, Catherine A., primary, Goettl, Virginia M., primary, Tran, Minh, primary, Harrington, Bonnie K., primary, Rogers, Kerry A., primary, Awan, Farrukh T., primary, Maddocks, Kami, primary, Andritsos, Leslie, primary, Lehman, Amy M., primary, Sampath, Deepa, primary, Lapalombella, Rosa, primary, Eathiraj, Sudharshan, primary, Abbadessa, Giovanni, primary, Schwartz, Brian, primary, Johnson, Amy J., primary, Byrd, John C., primary, and Woyach, Jennifer A., primary

Published
2023
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12. Supplementary Tables 4 and 5 from Eμ-TCL1xMyc: A Novel Mouse Model for Concurrent CLL and B-Cell Lymphoma

Author

Lucas, Fabienne, primary, Rogers, Kerry A., primary, Harrington, Bonnie K., primary, Pan, Alexander, primary, Yu, Lianbo, primary, Breitbach, Justin, primary, Bundschuh, Ralf, primary, Goettl, Virginia M., primary, Hing, Zachary A., primary, Kanga, Parviz, primary, Mantel, Rose, primary, Sampath, Deepa, primary, Smith, Lisa L., primary, Wasmuth, Ronni, primary, White, Danielle K., primary, Yan, Pearlly, primary, Byrd, John C., primary, Lapalombella, Rosa, primary, and Woyach, Jennifer A., primary

Published
2023
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13. Supplementary Data from Eμ-TCL1xMyc: A Novel Mouse Model for Concurrent CLL and B-Cell Lymphoma

Author

Lucas, Fabienne, primary, Rogers, Kerry A., primary, Harrington, Bonnie K., primary, Pan, Alexander, primary, Yu, Lianbo, primary, Breitbach, Justin, primary, Bundschuh, Ralf, primary, Goettl, Virginia M., primary, Hing, Zachary A., primary, Kanga, Parviz, primary, Mantel, Rose, primary, Sampath, Deepa, primary, Smith, Lisa L., primary, Wasmuth, Ronni, primary, White, Danielle K., primary, Yan, Pearlly, primary, Byrd, John C., primary, Lapalombella, Rosa, primary, and Woyach, Jennifer A., primary

Published
2023
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14. Supplementary Figure Legends from The Bruton Tyrosine Kinase (BTK) Inhibitor Acalabrutinib Demonstrates Potent On-Target Effects and Efficacy in Two Mouse Models of Chronic Lymphocytic Leukemia

Author

Herman, Sarah E.M., primary, Montraveta, Arnau, primary, Niemann, Carsten U., primary, Mora-Jensen, Helena, primary, Gulrajani, Michael, primary, Krantz, Fanny, primary, Mantel, Rose, primary, Smith, Lisa L., primary, McClanahan, Fabienne, primary, Harrington, Bonnie K., primary, Colomer, Dolors, primary, Covey, Todd, primary, Byrd, John C., primary, Izumi, Raquel, primary, Kaptein, Allard, primary, Ulrich, Roger, primary, Johnson, Amy J., primary, Lannutti, Brian J., primary, Wiestner, Adrian, primary, and Woyach, Jennifer A., primary

Published
2023
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15. Supplementary FiguresS1-5 from The Bruton Tyrosine Kinase (BTK) Inhibitor Acalabrutinib Demonstrates Potent On-Target Effects and Efficacy in Two Mouse Models of Chronic Lymphocytic Leukemia

Author

Herman, Sarah E.M., primary, Montraveta, Arnau, primary, Niemann, Carsten U., primary, Mora-Jensen, Helena, primary, Gulrajani, Michael, primary, Krantz, Fanny, primary, Mantel, Rose, primary, Smith, Lisa L., primary, McClanahan, Fabienne, primary, Harrington, Bonnie K., primary, Colomer, Dolors, primary, Covey, Todd, primary, Byrd, John C., primary, Izumi, Raquel, primary, Kaptein, Allard, primary, Ulrich, Roger, primary, Johnson, Amy J., primary, Lannutti, Brian J., primary, Wiestner, Adrian, primary, and Woyach, Jennifer A., primary

Published
2023
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16. The Multi-CDK Inhibitor Dinaciclib Shows Synergistic Activity with the BET Inhibitor PLX51107 and Reverses BET Resistance through Inhibition of Canonical Wnt Signaling in Acute Myeloid Leukemia (AML)

Author

Marr, Alexander, primary, Karmahapatra, Soumendrakrishna, additional, Corbin, Dominique, additional, Asemelash, Yerdanos, additional, Sher, Steven, additional, Mitchell, Shaneice Renee, additional, Harrington, Bonnie K, additional, Orwick, Shelley, additional, Beaver, Larry, additional, Wasmuth, Ronni, additional, Goettl, Virginia, additional, Mims, Alice S., additional, Larkin, Karilyn T., additional, Vasu, Sumithira, additional, Long, Meixiao, additional, Blachly, James S., additional, Garzon, Ramiro, additional, Byrd, John C., additional, Lapalombella, Rosa, additional, and Grieselhuber, Nicole, additional

Published
2022
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17. Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL)

Author

Woyach, Jennifer A., Bojnik, Engin, Ruppert, Amy S., Stefanovski, Matthew R., Goettl, Virginia M., Smucker, Kelly A., Smith, Lisa L., Dubovsky, Jason A., Towns, William H., MacMurray, Jessica, Harrington, Bonnie K., Davis, Melanie E., Gobessi, Stefania, Laurenti, Luca, Chang, Betty Y., Buggy, Joseph J., Efremov, Dimitar G., Byrd, John C., and Johnson, Amy J.

Published
2014
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18. Follicular Helper and Regulatory T Cells Drive the Development of Spontaneous Epstein–Barr Virus Lymphoproliferative Disorder.

Author

Ahmed, Elshafa Hassan, Lustberg, Mark, Hale, Claire, Sloan, Shelby, Mao, Charlene, Zhang, Xiaoli, Ozer, Hatice Gulcin, Schlotter, Sarah, Smith, Porsha L., Jeney, Frankie, Chan, Wing Keung, Harrington, Bonnie K., Weigel, Christoph, Brooks, Eric, Klimaszewski, Haley L., Oakes, Christopher C., Abebe, Tamrat, Ibrahim, Muntaser E., Alinari, Lapo, and Behbehani, Gregory K.

Subjects
BIOMARKERS, CYTOKINES, B cells, ANIMAL experimentation, IMMUNOCOMPROMISED patients, REGULATORY T cells, MYELOID-derived suppressor cells, EPSTEIN-Barr virus, RESEARCH funding, LYMPHOPROLIFERATIVE disorders, T cells, IMMUNOLOGIC memory, T helper cells, MICE
Abstract

Simple Summary: Over 90% of the adult population worldwide is infected with the Epstein–Barr virus (EBV). While EBV infection is associated with the development of lymphoproliferative disorders (EBV-LPD) in people with weakened immune systems, only ~20% of immunodeficient individuals develop EBV-LPD. Such clinical heterogeneity may reflect host variables that increase the risk of developing EBV-LPD. Immunodeficient mice engrafted with blood cells from EBV+ individuals develop spontaneous EBV-LPD of human B-cell origin with similar heterogeneity observed in humans. Our study aimed to investigate differences between the model's lymphoma producers (High-Incidence, HI donors) and non-lymphoma producers (No-Incidence, NI donors). HI donors showed high levels of T follicular helper (Tfh), regulatory T cells (Treg), and myeloid-derived suppressor cells compared to NI donors. Depletion of Tfh or Treg subsets delays or prevents EBV-LPD in this model. Our results reveal potential biomarkers that may help classify vulnerable patients at risk for developing EBV-LPD. Epstein–Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD. Engraftment of immunodeficient mice with peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive donors leads to spontaneous, malignant, human B-cell EBV-LPD. Only about 20% of EBV+ donors induce EBV-LPD in 100% of engrafted mice (High-Incidence, HI), while another 20% of donors never generate EBV-LPD (No-Incidence, NI). Here, we report HI donors to have significantly higher basal T follicular helper (Tfh) and regulatory T-cells (Treg), and depletion of these subsets prevents/delays EBV-LPD. Transcriptomic analysis of CD4+ T cells from ex vivo HI donor PBMC revealed amplified cytokine and inflammatory gene signatures. HI vs. NI donors showed a marked reduction in IFNγ production to EBV latent and lytic antigen stimulation. In addition, we observed abundant myeloid-derived suppressor cells in HI donor PBMC that decreased CTL proliferation in co-cultures with autologous EBV+ lymphoblasts. Our findings identify potential biomarkers that may identify individuals at risk for EBV-LPD and suggest possible strategies for prevention. [ABSTRACT FROM AUTHOR]

Published
2023
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21. DNA Origami Nanostructures Elicit Dose‐Dependent Immunogenicity and Are Nontoxic up to High Doses In Vivo

Author

Lucas, Christopher R., primary, Halley, Patrick D., additional, Chowdury, Amjad A., additional, Harrington, Bonnie K., additional, Beaver, Larry, additional, Lapalombella, Rosa, additional, Johnson, Amy J., additional, Hertlein, Erin K., additional, Phelps, Mitch A., additional, Byrd, John C., additional, and Castro, Carlos E., additional

Published
2022
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23. Targeting PRMT5 to Circumvent Acquired Ibrutinib Resistance in Mantle Cell Lymphoma

Author

Sloan, Shelby, primary, Brown, Fiona, additional, Chung, JI Hyun, additional, Prouty, Alexander, additional, Wheeler, Esther, additional, Harrington, Bonnie K, additional, Brooks, Eric, additional, Yilmaz, Ayse S, additional, Ozer, Hatice G, additional, Byrd, John C., additional, Chen-Kiang, Selina, additional, Di Liberto, Maurizio, additional, Lapalombella, Rosa, additional, Vaddi, Kris, additional, Scherle, Peggy, additional, Youssef, Youssef, additional, Baiocchi, Robert A, additional, and Alinari, Lapo, additional

Published
2019
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24. Eμ-TCL1xMyc: A Novel Mouse Model for Concurrent CLL and B-Cell Lymphoma

Author

Lucas, Fabienne, primary, Rogers, Kerry A., additional, Harrington, Bonnie K., additional, Pan, Alexander, additional, Yu, Lianbo, additional, Breitbach, Justin, additional, Bundschuh, Ralf, additional, Goettl, Virginia M., additional, Hing, Zachary A., additional, Kanga, Parviz, additional, Mantel, Rose, additional, Sampath, Deepa, additional, Smith, Lisa L., additional, Wasmuth, Ronni, additional, White, Danielle K., additional, Yan, Pearlly, additional, Byrd, John C., additional, Lapalombella, Rosa, additional, and Woyach, Jennifer A., additional

Published
2019
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25. Modulation of immune checkpoint molecule expression in mantle cell lymphoma

Author

Harrington, Bonnie K., primary, Wheeler, Esther, additional, Hornbuckle, Kasey, additional, Shana’ah, Arwa Y., additional, Youssef, Youssef, additional, Smith, Lisa, additional, Hassan II, Quais, additional, Klamer, Brett, additional, Zhang, Xiaoli, additional, Long, Meixiao, additional, Baiocchi, Robert A., additional, Maddocks, Kami, additional, Johnson, Amy J., additional, Byrd, John C., additional, and Alinari, Lapo, additional

Published
2019
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26. Anti–BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib

Author

McWilliams, Emily M., primary, Lucas, Christopher R., additional, Chen, Timothy, additional, Harrington, Bonnie K., additional, Wasmuth, Ronni, additional, Campbell, Amanda, additional, Rogers, Kerry A., additional, Cheney, Carolyn M., additional, Mo, Xiaokui, additional, Andritsos, Leslie A., additional, Awan, Farrukh T., additional, Woyach, Jennifer, additional, Carson, William E., additional, Butchar, Jonathan, additional, Tridandapani, Susheela, additional, Hertlein, Erin, additional, Castro, Carlos E., additional, Muthusamy, Natarajan, additional, and Byrd, John C., additional

Published
2019
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28. NAMPT Inhibitor KPT-9274 Selectively Targets Self-Renewal Capacity in Acute Myeloid Leukemia

Author

Mitchell, Shaneice Renee, primary, Grieselhuber, Nicole, additional, Asemelash, Yerdanos, additional, Cannon, Matthew, additional, Orwick, Shelley, additional, Sharma, Pratibha, additional, Goettl, Virginia, additional, Puduvalli, Vinay K, additional, Sampath, Deepa, additional, Mims, Alice S., additional, Blachly, James S., additional, Lehman, Amy M., additional, Harrington, Bonnie K., additional, Breitbach, Justin, additional, Baloglu, Erkan, additional, Senapedis, William, additional, Lapalombella, Rosa, additional, and Byrd, John C., additional

Published
2018
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29. PI3K p110δ inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression

Author

Dong, Shuai, primary, Harrington, Bonnie K., additional, Hu, Eileen Y., additional, Greene, Joseph T., additional, Lehman, Amy M., additional, Tran, Minh, additional, Wasmuth, Ronni L., additional, Long, Meixiao, additional, Muthusamy, Natarajan, additional, Brown, Jennifer R., additional, Johnson, Amy J., additional, and Byrd, John C., additional

Published
2018
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31. The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation

Author

Reiff, Sean D., primary, Mantel, Rose, additional, Smith, Lisa L., additional, Greene, J.T., additional, Muhowski, Elizabeth M., additional, Fabian, Catherine A., additional, Goettl, Virginia M., additional, Tran, Minh, additional, Harrington, Bonnie K., additional, Rogers, Kerry A., additional, Awan, Farrukh T., additional, Maddocks, Kami, additional, Andritsos, Leslie, additional, Lehman, Amy M., additional, Sampath, Deepa, additional, Lapalombella, Rosa, additional, Eathiraj, Sudharshan, additional, Abbadessa, Giovanni, additional, Schwartz, Brian, additional, Johnson, Amy J., additional, Byrd, John C., additional, and Woyach, Jennifer A., additional

Published
2018
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32. Anti-leukemic effects of all-trans retinoic acid in combination with Daratumumab in acute myeloid leukemia

Author

Buteyn, Nathaniel J, primary, Fatehchand, Kavin, additional, Santhanam, Ramasamy, additional, Fang, Huiqing, additional, Dettorre, Gino M, additional, Gautam, Shalini, additional, Harrington, Bonnie K, additional, Henderson, Sally E, additional, Merchand-Reyes, Giovanna, additional, Mo, Xiaokui, additional, Benson, Don M, additional, Carson, William E, additional, Vasu, Sumithira, additional, Byrd, John C, additional, Butchar, Jonathan P, additional, and Tridandapani, Susheela, additional

Published
2018
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33. BRAFV600E accelerates disease progression and enhances immune suppression in a mouse model of B-cell leukemia

Author

Tsai, Yo-Ting, primary, Lakshmanan, Aparna, additional, Lehman, Amy, additional, Harrington, Bonnie K., additional, Lucas, Fabienne McClanahan, additional, Tran, Minh, additional, Sass, Ellen J., additional, Long, Meixiao, additional, Flechtner, Alan D., additional, Jaynes, Florinda, additional, La Perle, Krista, additional, Coppola, Vincenzo, additional, Lozanski, Gerard, additional, Muthusamy, Natarajan, additional, Byrd, John C., additional, Grever, Michael R., additional, and Lucas, David M., additional

Published
2017
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34. Abstract 3014: BCL3 over-expression contributes anin vivogrowth advantage in a B-cell lymphoma xenograft model and is a risk factor for ibrutinib relapse in CLL

Author

Chen, Timothy L., primary, Harrington, Bonnie K., additional, Beaver, Larry, additional, Ruppert, Amy S., additional, Heerema, Nyla A., additional, Zhang, Xiaoli, additional, Ozer, Hatice Gulcin, additional, Johnson, Amy J., additional, Woyach, Jennifer A., additional, Hertlein, Erin, additional, and Byrd, John C., additional

Published
2017
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35. Abstract 1029: MAPK-mediated immunomodulation in disseminated murine Emu-TCL1 chronic lymphocytic leukemia

Author

Lakshmanan, Aparna, primary, Tsai, Yo-Ting, additional, Lehman, Amy, additional, Sass, Ellen J., additional, Tran, Minh, additional, Lucas, Fabienne, additional, Long, Meixiao, additional, Harrington, Bonnie K., additional, Perle, Krista La, additional, Coppola, Vincenzo, additional, Lozanski, Gerard, additional, Muthusamy, Natarajan, additional, Byrd, John C., additional, Grever, Michael R., additional, and Lucas, David M., additional

Published
2017
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36. The Bruton Tyrosine Kinase (BTK) Inhibitor Acalabrutinib Demonstrates Potent On-Target Effects and Efficacy in Two Mouse Models of Chronic Lymphocytic Leukemia

Author

Herman, Sarah E.M., primary, Montraveta, Arnau, additional, Niemann, Carsten U., additional, Mora-Jensen, Helena, additional, Gulrajani, Michael, additional, Krantz, Fanny, additional, Mantel, Rose, additional, Smith, Lisa L., additional, McClanahan, Fabienne, additional, Harrington, Bonnie K., additional, Colomer, Dolors, additional, Covey, Todd, additional, Byrd, John C., additional, Izumi, Raquel, additional, Kaptein, Allard, additional, Ulrich, Roger, additional, Johnson, Amy J., additional, Lannutti, Brian J., additional, Wiestner, Adrian, additional, and Woyach, Jennifer A., additional

Published
2017
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37. The Novel BET Inhibitor PLX51107 Has In Vitro and In Vivo Activity Against Acute Myeloid Leukemia

Author

Grieselhuber, Nicole R., primary, Mitchell, Shaneice R., additional, Orwick, Shelley, additional, Harrington, Bonnie K., additional, Goettl, Virginia M., additional, Walker, Alison R., additional, Bhatnagar, Bhavana, additional, Mims, Alice S., additional, Klisovic, Rebecca B., additional, Vasu, Sumithra, additional, Blum, William, additional, Blachly, James S., additional, Lucas, David M., additional, Garzon, Ramiro, additional, Lapalombella, Rosa, additional, and Byrd, John C., additional

Published
2016
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38. BRAFV600E Accelerates Disease Progression and Increases Immune Suppression in a Mouse Model of B-Cell Leukemia

Author

Tsai, Yo-Ting, primary, Lakshmanan, Aparna, additional, Lehman, Amy M., additional, Sass, Ellen J., additional, Tran, Minh, additional, McClanahan, Fabienne, additional, Long, Meixiao, additional, Harrington, Bonnie K., additional, La Perle, Krista, additional, Coppola, Vincenzo, additional, Lozanski, Gerard, additional, Muthusamy, Natarajan, additional, Byrd, John C., additional, Grever, Michael R., additional, and Lucas, David M., additional

Published
2016
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39. PI3K p110δ inactivation antagonizes chronic lymphocytic leukemia and reverses T cell immune suppression.

Author

Shuai Dong, Harrington, Bonnie K., Hu, Eileen Y., Greene, Joseph T., Lehman, Amy M., Minh Tran, Wasmuth, Ronni L., Meixiao Long, Muthusamy, Natarajan, Brown, Jennifer R., Johnson, Amy J., Byrd, John C., Dong, Shuai, Tran, Minh, and Long, Meixiao

Subjects
*LEUKEMIA, *T cells, *HEMATOLOGIC malignancies, *CHRONIC lymphocytic leukemia, *B cells
Abstract

Targeted therapy with small molecules directed at essential survival pathways in leukemia represents a major advance, including the phosphatidylinositol-3'-kinase (PI3K) p110δ inhibitor idelalisib. Here, we found that genetic inactivation of p110δ (p110δD910A/D910A) in the Eμ-TCL1 murine chronic lymphocytic leukemia (CLL) model impaired B cell receptor signaling and B cell migration, and significantly delayed leukemia pathogenesis. Regardless of TCL1 expression, p110δ inactivation led to rectal prolapse in mice resembling autoimmune colitis in patients receiving idelalisib. Moreover, we showed that p110δ inactivation in the microenvironment protected against CLL and acute myeloid leukemia. After receiving higher numbers of TCL1 leukemia cells, half of p110δD910A/D910A mice spontaneously recovered from high disease burden and resisted leukemia rechallenge. Despite disease resistance, p110δD910A/D910A mice exhibited compromised CD4+ and CD8+ T cell response, and depletion of CD4+ or CD8+ T cells restored leukemia. Interestingly, p110δD910A/D910A mice showed significantly impaired Treg expansion that associated with disease clearance. Reconstitution of p110δD910A/D910A mice with p110δWT/WT Tregs reversed leukemia resistance. Our findings suggest that p110δ inhibitors may have direct antileukemic and indirect immune-activating effects, further supporting that p110δ blockade may have a broader immune-modulatory role in types of leukemia that are not sensitive to p110δ inhibition. [ABSTRACT FROM AUTHOR]

Published
2019
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40. Development of a Fully Immunocompetent Adoptive Transfer In VivoModel of Npm1 cA;Idh2 R140Q;Flt3 ITDAML

Author

Sharpe, Chia, Johnson, Mariah, Fobare, Sydney, Elgamal, Ola A., Harrington, Bonnie K., Mustonen, Allison, Bryant, Kinsey, Cheney, Carolyn, Lerma, James R., Truxall, Jean, Furby, Casie, Long, Marissa, Fyock, Kaytlynn, Shih, Alan, Levine, Ross L, Hertlein, Erin K., and Byrd, John C.

Abstract

AML is a highly heterogeneous disease, both genetically and phenotypically. This includes both intra- and inter-patient heterogeneity that significantly impacts prognosis and treatment responses. Mouse models are a powerful tool to further our understanding of fundamental disease biology and to advance novel therapies. While human cell line (CDX) and primary patient (PDX) xenografts are reproducible in vivomodels, these models are by necessity immunodeficient. Transgenic mouse models provide an opportunity to study disease development driven by human relevant mutations within a fully immunocompetent system. However, drug development studies often require large numbers of mice and predictable time of disease development that is infeasible using primary transgenic animals. We therefore sought to develop a transgenic mouse model representative of human disease that was able to consistently be adoptively transferred into fully immunocompetent recipients.

Published
2023
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41. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma

Author

Harrington, Bonnie K., primary, Gardner, Heather L., additional, Izumi, Raquel, additional, Hamdy, Ahmed, additional, Rothbaum, Wayne, additional, Coombes, Kevin R., additional, Covey, Todd, additional, Kaptein, Allard, additional, Gulrajani, Michael, additional, Van Lith, Bart, additional, Krejsa, Cecile, additional, Coss, Christopher C., additional, Russell, Duncan S., additional, Zhang, Xiaoli, additional, Urie, Bridget K., additional, London, Cheryl A., additional, Byrd, John C., additional, Johnson, Amy J., additional, and Kisseberth, William C., additional

Published
2016
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42. The Bruton Tyrosine Kinase (BTK) Inhibitor ACP-196 Demonstrates Clinical Activity in Two Mouse Models of Chronic Lymphocytic Leukemia

Author

Herman, Sarah E. M., primary, Montraveta, Arnau, additional, Niemann, Carsten U, additional, Mora-Jensen, Helena, additional, Gulrajani, Michael, additional, Krantz, Fanny, additional, Harrington, Bonnie K., additional, Covey, Todd, additional, Lannutti, Brian J, additional, Izumi, Raquel, additional, Ulrich, Roger G, additional, Byrd, John C., additional, Wiestner, Adrian, additional, Johnson, Amy J., additional, and Woyach, Jennifer A., additional

Published
2015
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43. A Novel Inhibitor of BET Family Bromodomains Demonstrates In Vivo and I n Vi tro Potency in B-Cell Malignancies

Author

El-Gamal, Dalia, primary, Hing, Zachary A., additional, Mitchell, Shaneice, additional, LaFollette, Taylor D., additional, Brennan, Paul J., additional, Flynn, Joseph M., additional, Jones, Jeffrey A., additional, Awan, Farrukh, additional, Andritsos, Leslie A., additional, Blachly, James S., additional, Williams, Katie, additional, Harrington, Bonnie K., additional, Goettl, Virginia M., additional, Woyach, Jennifer A., additional, Lehman, Amy M., additional, Yu, Lianbo, additional, Byrd, John C., additional, and Lapalombella, Rosa, additional

Published
2015
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48. Abstract 2591: Ibrutinib can reverse established chronic graft-versus-host disease, which is dependent upon IL-2 inducible T-cell kinase (ITK) and Bruton's tyrosine kinase (BTK)-driven lymphocyte activation

Author

Dubovsky, Jason A., primary, Flynn, Ryan, additional, Du, Jing, additional, Harrington, Bonnie K., additional, Zhong, Yiming, additional, Yang, Carrie, additional, Towns, William, additional, Lehman, Amy, additional, Johnson, Amy, additional, Devine, Steven, additional, Jaglowski, Samantha, additional, Serody, Jonathan S., additional, Murphy, William J., additional, Munn, David H., additional, Luznik, Leo, additional, Hill, Geoffrey, additional, MacDonald, Kelli K.P., additional, Maillard, Ivan, additional, Koreth, John, additional, Cutler, Corey, additional, Soiffer, Robert J., additional, Antin, Joseph H., additional, Ritz, Jerome, additional, Panoskaltsis-Mortari, Angela, additional, Byrd, John C., additional, and Blazar, Bruce R., additional

Published
2014
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50. BRAFV600Eaccelerates disease progression and enhances immune suppression in a mouse model of B-cell leukemia

Author

Tsai, Yo-Ting, Lakshmanan, Aparna, Lehman, Amy, Harrington, Bonnie K., Lucas, Fabienne McClanahan, Tran, Minh, Sass, Ellen J., Long, Meixiao, Flechtner, Alan D., Jaynes, Florinda, La Perle, Krista, Coppola, Vincenzo, Lozanski, Gerard, Muthusamy, Natarajan, Byrd, John C., Grever, Michael R., and Lucas, David M.

Abstract

Mutated mitogen-activated protein kinase (MAPK) pathway components promote tumor survival, proliferation, and immune evasion in solid tumors. MAPK mutations occur in hematologic cancers as well, but their role is less clear and few models are available to study this. We developed an in vivo model of disseminated BRAFV600EB-cell leukemia to determine the effects of this mutation on tumor development and immune evasion. Mice with B-cell–restricted BRAFV600Eexpression crossed with the Eµ-TCL1 model of chronic lymphocytic leukemia (CLL) developed leukemia significantly earlier (median, 4.9 vs 8.1 months; P≮ .001) and had significantly shorter lifespan (median, 7.3 vs 12.1 months; P≮ .001) versus BRAF wild-type counterparts. BRAFV600Eexpression did not affect B-cell proliferation but reduced spontaneous apoptosis. BRAFV600E-mutant leukemia produced greater T-cell effects, evidenced by exhaustion immunophenotype and CD44+T-cell percentage, as well as increased expression of PD-L1 on CD11b+cells. Results were confirmed in syngeneic mice engrafted with BRAFV600Eleukemia cells. Furthermore, a BRAFV600E-expressing CLL cell line more strongly inhibited anti-CD3/CD28–induced T-cell proliferation, which was reversed by BRAFV600Einhibition. These results demonstrate the immune-suppressive impact of BRAFV600Ein B-cell leukemias and introduce a new model to develop rational combination strategies targeting both tumor cells and tumor-mediated immune evasion.

Published
2017
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