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3. Integrated single cell analysis reveals co-evolution of malignant B cells and tumor micro-environment in transformed follicular lymphoma

Author

Sarkozy, Clémentine, Wu, Shaocheng, Takata, Katsuyoshi, Aoki, Tomohiro, Neriah, Susana B., Milne, Katy, Goodyear, Talia, Strong, Celia, Rastogi, Tashi, Hilton, Laura K., Lai, Daniel, Sehn, Laurie H., Farinha, Pedro, Nelson, Brad H., Weng, Andrew, Marra, Marco, Scott, David W., Craig, Jeffrey W., Steidl, Christian, and Roth, Andrew

Published
2024
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4. Loss of glucocorticoid receptor expression mediates in vivo dexamethasone resistance in T-cell acute lymphoblastic leukemia

Author

Wandler, Anica M, Huang, Benjamin J, Craig, Jeffrey W, Hayes, Kathryn, Yan, Hannah, Meyer, Lauren K, Scacchetti, Alessandro, Monsalve, Gabriela, Dail, Monique, Li, Qing, Wong, Jasmine C, Weinberg, Olga, Hasserjian, Robert P, Kogan, Scott C, Jonsson, Philip, Yamamoto, Keith, Sampath, Deepak, Nakitandwe, Joy, Downing, James R, Zhang, Jinghui, Aster, Jon C, Taylor, Barry S, and Shannon, Kevin

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Rare Diseases, Childhood Leukemia, Pediatric, Pediatric Cancer, Orphan Drug, Genetics, Cancer, Hematology, 2.1 Biological and endogenous factors, Animals, Dexamethasone, Drug Resistance, Neoplasm, Humans, Indazoles, Male, Mice, Mice, Inbred C57BL, Mutation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Receptors, Glucocorticoid, Recurrence, Sulfonamides, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

Despite decades of clinical use, mechanisms of glucocorticoid resistance are poorly understood. We treated primary murine T lineage acute lymphoblastic leukemias (T-ALLs) with the glucocorticoid dexamethasone (DEX) alone and in combination with the pan-PI3 kinase inhibitor GDC-0941 and observed a robust response to DEX that was modestly enhanced by GDC-0941. Continuous in vivo treatment invariably resulted in outgrowth of drug-resistant clones, ~30% of which showed markedly reduced glucocorticoid receptor (GR) protein expression. A similar proportion of relapsed human T-ALLs also exhibited low GR protein levels. De novo or preexisting mutations in the gene encoding GR (Nr3c1) occurred in relapsed clones derived from multiple independent parental leukemias. CRISPR/Cas9 gene editing confirmed that loss of GR expression confers DEX resistance. Exposing drug-sensitive T-ALLs to DEX in vivo altered transcript levels of multiple genes, and this response was attenuated in relapsed T-ALLs. These data implicate reduced GR protein expression as a frequent cause of glucocorticoid resistance in T-ALL.

Published
2020

5. Molecular determinants of clinical outcomes in a real-world diffuse large B-cell lymphoma population

Author

Alduaij, Waleed, Collinge, Brett, Ben-Neriah, Susana, Jiang, Aixiang, Hilton, Laura K., Boyle, Merrill, Meissner, Barbara, Chong, Lauren, Miyata-Takata, Tomoko, Slack, Graham W., Farinha, Pedro, Craig, Jeffrey W., Lytle, Andrew, Savage, Kerry J., Villa, Diego, Gerrie, Alina S., Freeman, Ciara L., Gascoyne, Randy D., Connors, Joseph M., Morin, Ryan D., Sehn, Laurie H., Mungall, Andrew J., Steidl, Christian, and Scott, David W.

Published
2023
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7. Single-cell profiling reveals a memory B cell-like subtype of follicular lymphoma with increased transformation risk

Author

Wang, Xuehai, Nissen, Michael, Gracias, Deanne, Kusakabe, Manabu, Simkin, Guillermo, Jiang, Aixiang, Duns, Gerben, Sarkozy, Clementine, Hilton, Laura, Chavez, Elizabeth A., Segat, Gabriela C., Wong, Rachel, Kim, Jubin, Aoki, Tomohiro, Islam, Rashedul, May, Christina, Hung, Stacy, Tyshchenko, Kate, Brinkman, Ryan R., Hirst, Martin, Karsan, Aly, Freeman, Ciara, Sehn, Laurie H., Morin, Ryan D., Roth, Andrew J., Savage, Kerry J., Craig, Jeffrey W., Shah, Sohrab P., Steidl, Christian, Scott, David W., and Weng, Andrew P.

Published
2022
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9. Characterization of DLBCL with a PMBL gene expression signature

Author

Duns, Gerben, Viganò, Elena, Ennishi, Daisuke, Sarkozy, Clementine, Hung, Stacy S., Chavez, Elizabeth, Takata, Katsuyoshi, Rushton, Christopher, Jiang, Aixiang, Ben-Neriah, Susana, Woolcock, Bruce W., Slack, Graham W., Hsi, Eric D., Craig, Jeffrey W., Hilton, Laura K., Shah, Sohrab P., Farinha, Pedro, Mottok, Anja, Gascoyne, Randy D., Morin, Ryan D., Savage, Kerry J., Scott, David W., and Steidl, Christian

Published
2021
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10. The impact of MYC and BCL2 structural variants in tumors of DLBCL morphology and mechanisms of false-negative MYC IHC

Author

Collinge, Brett, Ben-Neriah, Susana, Chong, Lauren, Boyle, Merrill, Jiang, Aixiang, Miyata-Takata, Tomoko, Farinha, Pedro, Craig, Jeffrey W., Slack, Graham W., Ennishi, Daisuke, Mottok, Anja, Meissner, Barbara, Chavez, Elizabeth A., Gerrie, Alina S., Villa, Diego, Freeman, Ciara, Savage, Kerry J., Sehn, Laurie H., Morin, Ryan D., Mungall, Andrew J., Gascoyne, Randy D., Marra, Marco A., Connors, Joseph M., Steidl, Christian, and Scott, David W.

Published
2021
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13. Unbalanced MYCbreak-apart FISH patterns indicate the presence of a MYCrearrangement in HGBCL-DH-BCL2

Author

Collinge, Brett, Ben-Neriah, Susana, Hilton, Laura K., Alduaij, Waleed, Tucker, Tracy, Slack, Graham W., Farinha, Pedro, Craig, Jeffrey W., Boyle, Merrill, Meissner, Barbara, Villa, Diego, Gerrie, Alina S., Sehn, Laurie H., Savage, Kerry J., Morin, Ryan D., Mungall, Andrew J., Steidl, Christian, and Scott, David W.

Abstract

•Unbalanced MYCbreak-apart FISH patterns, in which red or green signal is lost, are observed in ∼13% of HGBCL-DH-BCL2tumors.•Balanced and unbalanced MYCrearrangements have the same biological consequences and should be reported as positive for rearrangement.

Published
2024
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16. DNA methyltransferase inhibition overcomes diphthamide pathway deficiencies underlying CD123-targeted treatment resistance

Author

Togami, Katsuhiro, Pastika, Timothy, Stephansky, Jason, Ghandi, Mahmoud, Christie, Amanda L., Jones, Kristen L., Johnson, Carl A., Lindsay, Ross W., Brooks, Christopher L., Letai, Anthony, Craig, Jeffrey W., Pozdnyakova, Olga, Weinstock, David M., Montero, Joan, Aster, Jon C., Johannessen, Cory M., and Lane, Andrew A.

Subjects
Thermo Fisher Scientific Inc., Interleukins, Blinatumomab, Methylation, Transferases, DNA, Dendritic cells, Inotuzumab ozogamicin, Scientific equipment industry, Tagraxofusp, Acute myelocytic leukemia, Cancer, Myeloid leukemia, Tumors, Genomes, Enzymes, Diphtheria, Health care industry
Abstract

The interleukin-3 receptor [alpha] subunit, CD123, is expressed in many hematologic malignancies including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload. Factors influencing response to tagraxofusp other than CD123 expression are largely unknown. We interrogated tagraxofusp resistance in patients and experimental models and found that it was not associated with CD123 loss. Rather, resistant AML and BPDCN cells frequently acquired deficiencies in the diphthamide synthesis pathway, impairing tagraxofusp's ability to ADP- ribosylate cellular targets. Expression of DPH1, encoding a diphthamide pathway enzyme, was reduced by DNA CpG methylation in resistant cells. Treatment with the DNA methyltransferase inhibitor azacitidine restored DPH1 expression and tagraxofusp sensitivity. We also developed a drug-dependent ADP-ribosylation assay in primary cells that correlated with tagraxofusp activity and may represent an additional novel biomarker. As predicted by these results and our observation that resistance also increased mitochondrial apoptotic priming, we found that the combination of tagraxofusp and azacitidine was effective in patient-derived xenografts treated in vivo. These data have important implications for clinical use of tagraxofusp and led to a phase 1 study combining tagraxofusp and azacitidine in myeloid malignancies., Introduction CD123, or the interleukin-3 (IL-3) receptor (IL-3R) [alpha] chain, is a cell-surface marker associated with a variety of hematologic malignancies and is often enriched on tumor cells compared with [...]

Published
2019
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18. Relapse Timing Is Associated With Distinct Evolutionary Dynamics in Diffuse Large B-Cell Lymphoma

Author

Hilton, Laura K., primary, Ngu, Henry S., additional, Collinge, Brett, additional, Dreval, Kostiantyn, additional, Ben-Neriah, Susana, additional, Rushton, Christopher K., additional, Wong, Jasper C.H., additional, Cruz, Manuela, additional, Roth, Andrew, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Slack, Graham W., additional, Farinha, Pedro, additional, Craig, Jeffrey W., additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Villa, Diego, additional, Rodrigo, Judith A., additional, Song, Kevin, additional, Crump, Michael, additional, Shepherd, Lois, additional, Hay, Annette E., additional, Kuruvilla, John, additional, Savage, Kerry J., additional, Kridel, Robert, additional, Karsan, Aly, additional, Marra, Marco A., additional, Sehn, Laurie H., additional, Steidl, Christian, additional, Morin, Ryan D., additional, and Scott, David W., additional

Published
2023
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20. Frontline therapy with bendamustine rituximab (BR) and rituximab cyclophosphamide vincristine prednisone (RCVP) confers similar long-term outcomes in patients with treatment naïve Waldenström macroglobulinemia in a real-world setting: a population-based analysis

Author

Kim, Jowon Laura, Gerrie, Alina S., Savage, Kerry Joane, Villa, Diego, Scott, David, Craig, Jeffrey W., Farinha, Pedro, Skinnider, Brian, Slack, Graham, Connors, Joseph M, Sehn, Laurie H., Venner, Christopher, and Freeman, Ciara L.

Subjects
RITUXIMAB, VINCRISTINE, RESOURCE-limited settings, PREDNISONE, PROGRESSION-free survival
Abstract

We report on outcomes of 111 patients with treatment naïve Waldenström macroglobulinemia (TN WM) treated with frontline bendamustine–rituximab (BR) (n = 57) or rituximab–cyclophosphamide–vincristine–prednisone (RCVP) (n = 54). Median follow-up was 60.7 months (range 1.9–231.6). Median progression-free survival (PFS) was 60.5 months (95% CI 47.6–73.4) for BR and 79.0 months (95% CI 31.3–126.8) for RCVP (p =.96). Median overall survival (OS) was not reached for BR and 153.4 months (95% CI 114.5–192.4) for RCVP (p =.37). While overall and major response rates did not differ between treatment groups, BR had numerically higher rate of very good partial response or better response (51% vs. 37%, p =.30) and complete response (26% vs. 13%, p =.13). RCVP confers comparable outcomes to BR in a real-world population of TN WM patients and remains an effective regimen, particularly when tolerance or frailty is an issue, or in resource-limited settings. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Supplementary Table 5 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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24. Supplementary Table 4 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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25. Supplementary Table 2 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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26. Data from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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27. Supplementary Table 6 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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28. Supplementary Table 3 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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29. Supplementary Table 7 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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30. Supplementary Table 1 from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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31. Supplementary Figures and Methods from Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents

Author

Lossos, Chen, primary, Liu, Yunpeng, primary, Kolb, Kellie E., primary, Christie, Amanda L., primary, Van Scoyk, Alexandria, primary, Prakadan, Sanjay M., primary, Shigemori, Kay, primary, Stevenson, Kristen E., primary, Morrow, Sara, primary, Plana, Olivia D., primary, Fraser, Cameron, primary, Jones, Kristen L., primary, Liu, Huiyun, primary, Pallasch, Christian P., primary, Modiste, Rebecca, primary, Nguyen, Quang-De, primary, Craig, Jeffrey W., primary, Morgan, Elizabeth A., primary, Vega, Francisco, primary, Aster, Jon C., primary, Sarosiek, Kristopher A., primary, Shalek, Alex K., primary, Hemann, Michael T., primary, and Weinstock, David M., primary

Published
2023
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32. Relapse timing is associated with distinct evolutionary dynamics in DLBCL

Author

Hilton, Laura K., primary, Ngu, Henry S., additional, Collinge, Brett, additional, Dreval, Kostiantyn, additional, Ben-Neriah, Susana, additional, Rushton, Christopher K., additional, Wong, Jasper C.H., additional, Cruz, Manuela, additional, Roth, Andrew, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Slack, Graham W., additional, Farinha, Pedro, additional, Craig, Jeffrey W., additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Villa, Diego, additional, Crump, Michael, additional, Shepherd, Lois, additional, Hay, Annette E., additional, Kuruvilla, John, additional, Savage, Kerry J., additional, Kridel, Robert, additional, Karsan, Aly, additional, Marra, Marco A., additional, Sehn, Laurie H., additional, Steidl, Christian, additional, Morin, Ryan D., additional, and Scott, David W., additional

Published
2023
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34. Integrated single cell analysis reveals co-evolution of malignant B cells and the tumor microenvironment in transformed follicular lymphoma

Author

Sarkozy, Clémentine, primary, Wu, Shaocheng, additional, Takata, Katsuyoshi, additional, Aoki, Tomohiro, additional, Neriah, Susana B, additional, Milne, Katy, additional, Goodyear, Talia, additional, Strong, Celia, additional, Rastogi, Tashi, additional, Lai, Daniel, additional, Sehn, Laurie H, additional, Farinha, Pedro, additional, Nelson, Brad H, additional, Weng, Andrew, additional, Scott, David W, additional, Craig, Jeffrey W, additional, Steidl, Christian, additional, and Roth, Andrew, additional

Published
2022
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35. Do Unbalanced MYC Break-Apart FISH Patterns Indicate the Presence of a MYC Rearrangement?

Author

Collinge, Brett, primary, Ben-Neriah, Susana, additional, Hilton, Laura K, additional, Alduaij, Waleed, additional, Tucker, Tracy, additional, Slack, Graham W, additional, Farinha, Pedro, additional, Craig, Jeffrey W., additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Mekwunye, Kelly, additional, Villa, Diego, additional, Gerrie, Alina S., additional, Sehn, Laurie H., additional, Savage, Kerry J., additional, Morin, Ryan D., additional, Mungall, Andrew J., additional, Steidl, Christian, additional, and Scott, David W., additional

Published
2022
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36. Relapse Timing Is Associated with Distinct Evolutionary Dynamics and Response to Salvage Therapy in DLBCL

Author

Hilton, Laura K, primary, Ngu, Henry S., additional, Collinge, Brett, additional, Dreval, Kostiantyn, additional, Ben-Neriah, Susana, additional, Rushton, Christopher K, additional, Wong, Jasper, additional, Cruz, Manuela, additional, Roth, Andrew, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Slack, Graham W., additional, Farinha, Pedro, additional, Craig, Jeffrey W., additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Villa, Diego, additional, Savage, Kerry J., additional, Sehn, Laurie H., additional, Marra, Marco A., additional, Karsan, Aly, additional, Steidl, Christian, additional, Morin, Ryan D., additional, and Scott, David W., additional

Published
2022
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37. Long-Term Outcomes of Patients Aged 65 Years or Older with Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) and T-Follicular Helper T-Cell Lymphoma (TFHTCL) Treated with Curative Intent CHOP(like) Chemotherapy

Author

Ngu, Henry S., primary, Villa, Diego, additional, Gerrie, Alina S., additional, Venner, Christopher P., additional, Lytle, Andrew, additional, Skinnider, Brian, additional, Craig, Jeffrey W., additional, Slack, Graham W., additional, Scott, David W., additional, Sehn, Laurie H., additional, and Savage, Kerry J., additional

Published
2022
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38. Genetic Determinants of Isolated and Systemic Testicular Diffuse Large B-Cell Lymphoma Highlight a Disease Spectrum

Author

Wong, Jasper, primary, Collinge, Brett, additional, Hilton, Laura K, additional, Ben-Neriah, Susana, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Mekwunye, Kelly, additional, Slack, Graham W., additional, Farinha, Pedro, additional, Craig, Jeffrey W., additional, Sehn, Laurie H., additional, Villa, Diego, additional, Gerrie, Alina S., additional, Mungall, Andrew J., additional, Steidl, Christian, additional, Cook, James R., additional, Feldman, Andrew L., additional, Rimsza, Lisa M., additional, Savage, Kerry J., additional, Morin, Ryan D., additional, and Scott, David W., additional

Published
2022
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39. Risk of Central Nervous System Involvement in High-Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements: Analysis of a Population-Based Cohort with Routine Fluorescence in Situ Hybridization Testing in British Columbia

Author

Alduaij, Waleed, primary, Jiang, Aixiang, additional, Villa, Diego, additional, Collinge, Brett, additional, Ben-Neriah, Susana, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Hilton, Laura K, additional, Farinha, Pedro, additional, Slack, Graham W, additional, Craig, Jeffrey W., additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Mungall, Andrew J., additional, Steidl, Christian, additional, Sehn, Laurie H., additional, Scott, David W., additional, and Savage, Kerry J., additional

Published
2022
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41. Molecular Determinants of Clinical Outcomes In a Real-World Diffuse Large B-cell Lymphoma Population

Author

Alduaij, Waleed, primary, Collinge, Brett J, additional, Ben-Neriah, Susana, additional, Jiang, Aixiang, additional, Hilton, Laura K, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Chong, Lauren C., additional, Miyata-Takata, Tomoko, additional, Slack, Graham W., additional, Farinha, Pedro, additional, Craig, Jeffrey W, additional, Lytle, Andrew, additional, Savage, Kerry J., additional, Villa, Diego, additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Gascoyne, Randy D., additional, Connors, Joseph M, additional, Morin, Ryan D, additional, Sehn, Laurie H., additional, Mungall, Andrew J, additional, Steidl, Christian, additional, and Scott, David W., additional

Published
2022
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42. Abstract A19: Integrated single cell analysis reveals co-evolution of malignant B cells and the tumor microenvironment in transformed follicular lymphoma

Author

Sarkozy, Clementine, primary, Wu, Shaocheng, additional, Takata, Katsuyoshi, additional, Aoki, Tomohiro, additional, Neriah, Susana B, additional, Milne, Katy, additional, Nelson, Brad, additional, Weng, Andrew, additional, Scott, David, additional, Craig, Jeffrey W, additional, Steidl, Christian, additional, and Roth, Andrew, additional

Published
2022
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45. Immune Profiling of Diagnostic DLBCL Biopsies Dramatically Improves upon Cell-of-Origin Risk Stratification

Author

Nissen, Michael, primary, Wang, Xuehai, additional, Sarkozy, Clementine, additional, Jiang, Aixiang, additional, Ennishi, Daisuke, additional, Aoki, Tomohiro, additional, Hung, Stacy, additional, Chavez, Elizabeth, additional, Craig, Jeffrey W, additional, Farinha, Pedro, additional, Slack, Graham W., additional, Scott, David W., additional, Steidl, Christian, additional, and Weng, Andrew P., additional

Published
2021
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46. Single-Cell Profiling Reveals Clinically Relevant Evolutionary Trajectories and Alternate Biologies in Human Follicular Lymphoma

Author

Wang, Xuehai, primary, Nissen, Michael, additional, Gracias, Deanne, additional, Kusakabe, Manabu, additional, Simkin, Guillermo, additional, Duns, Gerben, additional, Sarkozy, Clementine, additional, Chavez, Elizabeth, additional, Segat, Gabriela Cristina, additional, Kim, Jubin, additional, Jiang, Aixiang, additional, Aoki, Tomohiro, additional, Islam, Rashedul, additional, May, Christina, additional, Hung, Stacy, additional, Tyshchenko, Kateryna, additional, Brinkman, Ryan, additional, Hirst, Martin, additional, Karsan, Aly, additional, Freeman, Ciara L., additional, Sehn, Laurie H., additional, Savage, Kerry J., additional, Craig, Jeffrey W, additional, Scott, David W., additional, Steidl, Christian, additional, Shah, Sohrab P, additional, and Weng, Andrew P., additional

Published
2021
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47. Frontline Therapy with Bendamustine-Rituximab (BR) in Patients with Treatment-Naïve Waldenstrom's Macroglobulinemia Confers Similar Long-Term Outcomes to R-CVP in a Real-World Setting: A Population-Based Analysis

Author

Kim, Jowon Laura, primary, Gerrie, Alina S., additional, Savage, Kerry J., additional, Villa, Diego, additional, Scott, David W., additional, Craig, Jeffrey W, additional, Farinha, Pedro, additional, Skinnider, Brian, additional, Slack, Graham W., additional, Connors, Joseph M., additional, Sehn, Laurie H., additional, and Freeman, Ciara L., additional

Published
2021
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48. Population-Wide Introduction of Dose-Adjusted EPOCH-R Is Associated with Improved Outcome of High Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements with Diffuse Large B-Cell Lymphoma Morphology

Author

Alduaij, Waleed, primary, Sehn, Laurie H., additional, Jiang, Aixiang, additional, Ben-Neriah, Susana, additional, Collinge, Brett, additional, Hilton, Laura K, additional, Boyle, Merrill, additional, Meissner, Barbara, additional, Farinha, Pedro, additional, Slack, Graham W., additional, Craig, Jeffrey W, additional, Miyata-Takata, Tomoko, additional, Villa, Diego, additional, Gerrie, Alina S., additional, Freeman, Ciara L., additional, Savage, Kerry J., additional, Gascoyne, Randy D., additional, Connors, Joseph M., additional, Mungall, Andrew J., additional, Steidl, Christian, additional, and Scott, David W., additional

Published
2021
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49. Mechanisms of lymphoma clearance induced by high-dose alkylating agents

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Ragon Institute of MGH, MIT and Harvard, Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E, Christie, Amanda L, van Scoyk, Alexandria, Prakadan, Sanjay M, Shigemori, Kay, Stevenson, Kristen E, Morrow, Sara, Plana, Olivia D, Fraser, Cameron, Jones, Kristen L, Liu, Huiyun, Pallasch, Christian P, Modiste, Rebecca, Nguyen, Quang-De, Craig, Jeffrey W, Morgan, Elizabeth A, Vega, Francisco, Aster, Jon C, Sarosiek, Kristopher A, Shalek, Alex K, Hemann, Michael T, Weinstock, David M, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Chemistry, Ragon Institute of MGH, MIT and Harvard, Lossos, Chen, Liu, Yunpeng, Kolb, Kellie E, Christie, Amanda L, van Scoyk, Alexandria, Prakadan, Sanjay M, Shigemori, Kay, Stevenson, Kristen E, Morrow, Sara, Plana, Olivia D, Fraser, Cameron, Jones, Kristen L, Liu, Huiyun, Pallasch, Christian P, Modiste, Rebecca, Nguyen, Quang-De, Craig, Jeffrey W, Morgan, Elizabeth A, Vega, Francisco, Aster, Jon C, Sarosiek, Kristopher A, Shalek, Alex K, Hemann, Michael T, and Weinstock, David M

Abstract

© 2019 American Association for Cancer Research. The extraordinary activity of high-dose cyclophosphamide against some high-grade lymphomas was described nearly 60 years ago. Here we address mechanisms that mediate cyclophosphamide activity in bona fide human double-hit lymphoma. We show that antibody resistance within the bone marrow (BM) is not present upon early engraftment but develops during lymphoma progression. This resistance required a high tumor:macrophage ratio, was recapitulated in spleen by partial macrophage depletion, and was overcome by multiple, high-dose alkylating agents. Cyclophosphamide induced endoplasmic reticulum (ER) stress in BM-resident lymphoma cells in vivo that resulted in ATF4-mediated paracrine secretion of VEGFA, massive macrophage infiltration, and clearance of alemtuzumab-opsonized cells. BM macrophages isolated after cyclophosphamide treatment had increased phagocytic capacity that was reversed by VEGFA blockade or SYK inhibition. Single-cell RNA sequencing of these macrophages identified a “super-phagocytic” subset that expressed CD36/FCGR4. Together, these findings define a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance. SIGNIFICANCE: mAbs are effective against only a small subset of cancers. Herein, we recapitulate compartment-specific antibody resistance and define an ER stress–dependent mechanism induced by high-dose alkylating agents that promotes phagocytosis of opsonized tumor cells. This approach induces synergistic effects with mAbs and merits testing across additional tumor types.

Published
2021

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