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444 results on '"Chan, Steven M"'

1. Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms

Author

Murphy, Tracy, Mason, Jacqueline M., Leber, Brian, Bray, Mark R., Chan, Steven M., Gupta, Vikas, Khalaf, Dina, Maze, Dawn, McNamara, Caroline J., Schimmer, Aaron D., Schuh, Andre C., Sibai, Hassan, Trus, Michael, Valiquette, Debbie, Martin, Kylie, Nguyen, Linh, Li, Xuan, Mak, Tak W., Minden, Mark D., and Yee, Karen W. L.

Published
2024
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2. Information-theoretic multi-time-scale partially observable systems with inspiration from leukemia treatment

Author

Chapman, Margaret P., Jensen, Emily, Chan, Steven M., and Lessard, Laurent

Subjects
Electrical Engineering and Systems Science - Systems and Control
Abstract

We study a partially observable nonlinear stochastic system with unknown parameters, where the given time scales of the states and measurements may be distinct. The proposed setting is inspired by disease management, particularly leukemia.

Published
2022
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3. Asparaginase completion among adults including older patients with acute lymphoblastic leukemia treated with a modified DFCI protocol

Author

Perusini, Maria Agustina, Andrews, Claire, Eshetu, Atenafu G., Gupta, Vikas, Maze, Dawn, Yee, Karen W. L., Bankar, Aniket, Davidson, Marta B., Richard-Carpentier, Guillaume, Chan, Steven M., Schimmer, Aaron D., Sibai, Jad, Alharbi, Salman, Lucero, Josephine A., Linn, Swe Mar, Minden, Mark D., Schuh, Andre C., and Sibai, Hassan

Published
2024
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6. Optimizing survival outcomes with post‐remission therapy in acute myeloid leukemia

Author

Medeiros, Bruno C, Chan, Steven M, Daver, Naval G, Jonas, Brian A, and Pollyea, Daniel A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Genetics, Pediatric Cancer, Cancer, Childhood Leukemia, Clinical Research, Hematology, Biotechnology, Pediatric, Pediatric Research Initiative, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Detection, screening and diagnosis, Good Health and Well Being, Humans, Leukemia, Myeloid, Acute, Neoplasm, Residual, Recurrence, Remission Induction, Cardiorespiratory Medicine and Haematology, Immunology, Cardiovascular medicine and haematology
Abstract

Optimization of post-remission therapies to maintain complete remission and prevent relapse is a major challenge in treating patients with acute myeloid leukemia (AML). Monitoring patients for measurable residual disease (MRD) is helpful to identify those at risk for relapse. Hypomethylating agents are being investigated as post-remission therapy. Identification of recurrent genetic alterations that drive disease progression has enabled the design of new, personalized approaches to therapy for patients with AML. Emerging data suggest that targeted post-remission therapy, alone or in combination with chemotherapy, may improve outcomes. Results of ongoing clinical trials will further define potential clinical benefits.

Published
2019

9. Outcomes of intensive and nonintensive blast-reduction strategies in accelerated and blast-phase MPN

Author

Davidson, Marta B, primary, Kennedy, James A, additional, Capo-Chichi, Jose-Mario, additional, Shi, Yuliang, additional, Xu, Wei, additional, Cheung, Verna, additional, Arruda, Andrea, additional, Bankar, Aniket, additional, Richard-Carpentier, Guillaume, additional, Chan, Steven M., additional, Maze, Dawn, additional, Minden, Mark D, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Sibai, Hassan, additional, Yee, Karen W.L., additional, Tierens, Anne, additional, VISWABANDYA, AURO, additional, and Gupta, Vikas, additional

Published
2024
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10. Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms

Author

Murphy, Tracy, primary, Mason, Jacqueline M., additional, Leber, Brian, additional, Bray, Mark R., additional, Chan, Steven M., additional, Gupta, Vikas, additional, Khalaf, Dina, additional, Maze, Dawn, additional, McNamara, Caroline J., additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Sibai, Hassan, additional, Trus, Michael, additional, Valiquette, Debbie, additional, Martin, Kylie, additional, Nguyen, Linh, additional, Li, Xuan, additional, Mak, Tak W., additional, Minden, Mark D., additional, and Yee, Karen W. L., additional

Published
2023
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12. AML refractory to primary induction with Ida-FLAG has a poor clinical outcome

Author

Kavanagh, Simon, Heath, Emily, Hurren, Rose, Gronda, Marcela, Barghout, Samir H., Liyanage, Sanduni U., Siriwardena, Thirushi P., Claudio, Jaime, Zhang, Tong, Sukhai, Mahadeo, Stockley, Tracy L., Kamel-Reid, Suzanne, Rostom, Amr, Lutynski, Andrzej, Khalaf, Dina, Rydlewski, Anna, Chan, Steven M., Gupta, Vikas, Maze, Dawn, Sibai, Hassan, Schuh, Andre C., Yee, Karen, Minden, Mark D., and Schimmer, Aaron D.

Published
2018
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14. Supplementary Table S6 from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs

Author

Dobson, Stephanie M., primary, García-Prat, Laura, primary, Vanner, Robert J., primary, Wintersinger, Jeffrey, primary, Waanders, Esmé, primary, Gu, Zhaohui, primary, McLeod, Jessica, primary, Gan, Olga I., primary, Grandal, Ildiko, primary, Payne-Turner, Debbie, primary, Edmonson, Michael N., primary, Ma, Xiaotu, primary, Fan, Yiping, primary, Voisin, Veronique, primary, Chan-Seng-Yue, Michelle, primary, Xie, Stephanie Z., primary, Hosseini, Mohsen, primary, Abelson, Sagi, primary, Gupta, Pankaj, primary, Rusch, Michael, primary, Shao, Ying, primary, Olsen, Scott R., primary, Neale, Geoffrey, primary, Chan, Steven M., primary, Bader, Gary, primary, Easton, John, primary, Guidos, Cynthia J., primary, Danska, Jayne S., primary, Zhang, Jinghui, primary, Minden, Mark D., primary, Morris, Quaid, primary, Mullighan, Charles G., primary, and Dick, John E., primary

Published
2023
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15. Supplementary Table S3: Median Survival By Cluster from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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16. Data from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs

Author

Dobson, Stephanie M., primary, García-Prat, Laura, primary, Vanner, Robert J., primary, Wintersinger, Jeffrey, primary, Waanders, Esmé, primary, Gu, Zhaohui, primary, McLeod, Jessica, primary, Gan, Olga I., primary, Grandal, Ildiko, primary, Payne-Turner, Debbie, primary, Edmonson, Michael N., primary, Ma, Xiaotu, primary, Fan, Yiping, primary, Voisin, Veronique, primary, Chan-Seng-Yue, Michelle, primary, Xie, Stephanie Z., primary, Hosseini, Mohsen, primary, Abelson, Sagi, primary, Gupta, Pankaj, primary, Rusch, Michael, primary, Shao, Ying, primary, Olsen, Scott R., primary, Neale, Geoffrey, primary, Chan, Steven M., primary, Bader, Gary, primary, Easton, John, primary, Guidos, Cynthia J., primary, Danska, Jayne S., primary, Zhang, Jinghui, primary, Minden, Mark D., primary, Morris, Quaid, primary, Mullighan, Charles G., primary, and Dick, John E., primary

Published
2023
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17. Supplementary Table S2: mRNA Cluster Signatures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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18. Supplementary Table S1: Sample mutations from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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19. Supplementary Table S4: Enhancer, mRNA, and SY-1425 EC50 in AML cell lines from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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20. Supplementary Methods and Figure Legends from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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21. Supplementary Table S7: GREAT analysis from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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22. Data from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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23. Supplementary Figures S1-S11 from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs

Author

Dobson, Stephanie M., primary, García-Prat, Laura, primary, Vanner, Robert J., primary, Wintersinger, Jeffrey, primary, Waanders, Esmé, primary, Gu, Zhaohui, primary, McLeod, Jessica, primary, Gan, Olga I., primary, Grandal, Ildiko, primary, Payne-Turner, Debbie, primary, Edmonson, Michael N., primary, Ma, Xiaotu, primary, Fan, Yiping, primary, Voisin, Veronique, primary, Chan-Seng-Yue, Michelle, primary, Xie, Stephanie Z., primary, Hosseini, Mohsen, primary, Abelson, Sagi, primary, Gupta, Pankaj, primary, Rusch, Michael, primary, Shao, Ying, primary, Olsen, Scott R., primary, Neale, Geoffrey, primary, Chan, Steven M., primary, Bader, Gary, primary, Easton, John, primary, Guidos, Cynthia J., primary, Danska, Jayne S., primary, Zhang, Jinghui, primary, Minden, Mark D., primary, Morris, Quaid, primary, Mullighan, Charles G., primary, and Dick, John E., primary

Published
2023
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24. Supplementary Figures from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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25. Supplementary Table S5 & 6: GSEA of SY-1425 response from Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist

Author

McKeown, Michael R., primary, Corces, M. Ryan, primary, Eaton, Matthew L., primary, Fiore, Chris, primary, Lee, Emily, primary, Lopez, Jeremy T., primary, Chen, Mei Wei, primary, Smith, Darren, primary, Chan, Steven M., primary, Koenig, Julie L., primary, Austgen, Kathryn, primary, Guenther, Matthew G., primary, Orlando, David A., primary, Lovén, Jakob, primary, Fritz, Christian C., primary, and Majeti, Ravindra, primary

Published
2023
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32. Do Adult Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Patients Require Allogeneic Transplant in First Remission (CR1)?

Author

Khadadah, Fatima M, primary, Andrews, Claire, additional, Atenafu, Eshetu G., additional, Schuh, Andre C., additional, Maze, Dawn, additional, Yee, Karen, additional, Jarallah, Osamah Jamal S., additional, Minden, Mark D., additional, Schimmer, Aaron D., additional, Chan, Steven M., additional, Gupta, Vikas, additional, Kim, Dennis Dong Hwan, additional, and Sibai, Hassan, additional

Published
2022
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33. Uncovering Distinct Metabolic Properties of Relapse and Relapse-Fated Clones in B-Cell Acute Lymphoblastic Leukemia

Author

Smith, Sabrina A, primary, Garcia Prat, Laura, additional, Hosseini, Mohsen, additional, Jin, Liqing, additional, Mbong, Nathan, additional, Doedens, Monica, additional, McLeod, Jessica, additional, Reisz, Julie A., additional, Wilkerson, Rebecca, additional, D'Alessandro, Angelo, additional, Chan, Steven M., additional, Jones, Courtney L, additional, and Dick, John E., additional

Published
2022
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34. Clinical Outcomes in De Novo Versus Secondary NPM1-Mutated AML

Author

Smith, Elliot C., primary, Atenafu, Eshetu G., additional, Bankar, Aniket, additional, Chan, Steven M., additional, Davidson, Marta B., additional, Gupta, Vikas, additional, Minden, Mark D., additional, Richard-Carpentier, Guillaume, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Sibai, Hassan, additional, Yee, Karen, additional, and Maze, Dawn, additional

Published
2022
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35. Acute Lymphoblastic Leukemia in Patients 60 Years and Older Treated with Pediatric-Inspired Protocols, 20 Years of Follow-up

Author

Perusini, Maria Agustina, primary, Atenafu, Eshetu G., additional, Bankar, Aniket, additional, Gupta, Vikas, additional, Minden, Mark D., additional, Sibai, Jad, additional, Maze, Dawn, additional, Davidson, Marta B., additional, Chan, Steven M., additional, Binder, Fernando, additional, Richard-Carpentier, Guillaume, additional, Alharbi, Salman, additional, Andrews, Claire, additional, Yee, Karen, additional, Schuh, Andre C., additional, and Sibai, Hassan, additional

Published
2022
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37. Real-World Outcomes and Adverse Events of Elderly Patients with Ph-Negative Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Protocol

Author

Perusini, Maria Agustina, primary, Sibai, Jad, additional, Atenafu, Eshetu G., additional, Bankar, Aniket, additional, Minden, Mark D., additional, Gupta, Vikas, additional, Maze, Dawn, additional, Davidson, Marta B., additional, Chan, Steven M., additional, Schimmer, Aaron D., additional, Richard-Carpentier, Guillaume, additional, Lucero, Josephine Anne, additional, Andrews, Claire, additional, Kim, Dennis Dong Hwan, additional, Yee, Karen, additional, Schuh, Andre C., additional, and Sibai, Hassan, additional

Published
2022
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39. Outcome of ALL in Adult Patient with Down Syndrome, Single Center Experience

Author

Alharbi, Salman, primary, Perusini, Maria Agustina, additional, Bhella, Sita, additional, Minden, Mark D., additional, Maze, Dawn, additional, Gupta, Vikas, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Yee, Karen, additional, Chan, Steven M., additional, Bankar, Aniket, additional, Davidson, Marta B., additional, Richard-Carpentier, Guillaume, additional, Sibai, Jad, additional, and Sibai, Hassan, additional

Published
2022
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40. Clinical and Biological Characteristics and Outcomes of Therapy-Related Acute Lymphoblastic Leukemia (t-ALL) Following Multiple Myeloma Are Distinct in Comparison to t-ALL Following Other Cancers

Author

Lucero, Josephine Anne, primary, Merchán, Brayan, additional, Jarallah, Osamah Jamal S., additional, Bankar, Aniket, additional, Chan, Steven M., additional, Davidson, Marta B., additional, Gupta, Vikas, additional, Maze, Dawn, additional, Minden, Mark D., additional, Richard-Carpentier, Guillaume, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Yee, Karen, additional, and Sibai, Hassan, additional

Published
2022
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41. Multiparameter Flow Cytometry-Based Residual Disease Analysis Identifies Intermediate-Risk AML Patients Who May Benefit from Allogeneic Hematopoietic Stem Cell Transplantation

Author

Lucero, Josephine Anne, primary, Tierens, Anne, additional, Alhumaid, Muhned, additional, Capo-Chichi, Jose-Mario, additional, Stockley, Tracy L., additional, Gupta, Vikas, additional, Chan, Steven M., additional, Schuh, Andre C., additional, Minden, Mark D., additional, Mattsson, Jonas, additional, Kumar, Rajat, additional, Sibai, Hassan, additional, and Kim, Dennis Dong Hwan, additional

Published
2022
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43. Single Centre, Retrospective Analysis of Treatment Outcomes and Prognostic Factors in Blastic Phase Chronic Myeloid Leukemia (CML-BP) Following Systemic Therapy

Author

Tang, Kenny, primary, Maze, Dawn, additional, Yee, Karen, additional, Sibai, Hassan, additional, Davidson, Marta B., additional, Chan, Steven M., additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Bankar, Aniket, additional, Richard-Carpentier, Guillaume, additional, Tierens, Anne, additional, Minden, Mark D., additional, Gupta, Vikas, additional, Lipton, Jeffrey H., additional, and Kim, Dennis, additional

Published
2022
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44. Safety of re‐challenging adults with acute lymphoblastic leukemia with PEG‐asparaginase‐induced severe hypertriglyceridemia when treated with a pediatric‐inspired regimen

Author

Al Nabhani, Ibrahim, primary, Andrews, Claire, additional, Sibai, Jad, additional, Atenafu, Eshetu, additional, Young, Taylor, additional, Chan, Steven M., additional, Gupta, Vikas, additional, Maze, Dawn, additional, Schimmer, Aaron D., additional, Schuh, Andre C., additional, Yee, Karen, additional, and Sibai, Hassan, additional

Published
2022
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48. Information-theoretic multi-time-scale partially observable systems with relevance to leukemia treatment

Author

Chapman, Margaret P., Jensen, Emily, Chan, Steven M., and Lessard, Laurent

Subjects
FOS: Electrical engineering, electronic engineering, information engineering, Systems and Control (eess.SY), Electrical Engineering and Systems Science - Systems and Control
Abstract

Inspired by a leukemia treatment challenge, we study a partially observable non-linear stochastic system with unknown parameters, where the given time scales of the states and measurements may be distinct. Key words: Stochastic control; Non-linear systems; Partially observable systems; System identification; Biomedical systems., under review for Automatica

Published
2022

49. Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target

Author

Vanner, Robert J., Dobson, Stephanie M., Gan, Olga I., McLeod, Jessica, Schoof, Erwin M., Grandal, Ildiko, Wintersinger, Jeff A., Garcia-Prat, Laura, Hosseini, Mohsen, Xie, Stephanie Z., Jin, Liqing, Mbong, Nathan, Voisin, Veronique, Chan-Seng-Yue, Michelle, Kennedy, James A., Waanders, Esmé, Morris, Quaid, Porse, Bo, Chan, Steven M., Guidos, Cynthia J., Danska, Jayne S., Minden, Mark D., Mullighan, Charles G., Dick, John E., Vanner, Robert J., Dobson, Stephanie M., Gan, Olga I., McLeod, Jessica, Schoof, Erwin M., Grandal, Ildiko, Wintersinger, Jeff A., Garcia-Prat, Laura, Hosseini, Mohsen, Xie, Stephanie Z., Jin, Liqing, Mbong, Nathan, Voisin, Veronique, Chan-Seng-Yue, Michelle, Kennedy, James A., Waanders, Esmé, Morris, Quaid, Porse, Bo, Chan, Steven M., Guidos, Cynthia J., Danska, Jayne S., Minden, Mark D., Mullighan, Charles G., and Dick, John E.

Abstract

Central nervous system (CNS) dissemination of B-precursor acute lymphoblastic leukemia (B-ALL) has poor prognosis and remains a therapeutic challenge. Here we performed targeted DNA sequencing as well as transcriptional and proteomic profiling of paired leukemia-infiltrating cells in the bone marrow (BM) and CNS of xenografts. Genes governing mRNA translation were upregulated in CNS leukemia, and subclonal genetic profiling confirmed this in both BM-concordant and BM-discordant CNS mutational populations. CNS leukemia cells were exquisitely sensitive to the translation inhibitor omacetaxine mepesuccinate, which reduced xenograft leptomeningeal disease burden. Proteomics demonstrated greater abundance of secreted proteins in CNS-infiltrating cells, including complement component 3 (C3), and drug targeting of C3 influenced CNS disease in xenografts. CNS-infiltrating cells also exhibited selection for stemness traits and metabolic reprogramming. Overall, our study identifies targeting of mRNA translation as a potential therapeutic approach for B-ALL leptomeningeal disease. SIGNIFICANCE: Cancer metastases are often driven by distinct subclones with unique biological properties. Here we show that in B-ALL CNS disease, the leptomeningeal environment selects for cells with unique functional dependencies. Pharmacologic inhibition of mRNA translation signaling treats CNS disease and offers a new therapeutic approach for this condition.This article is highlighted in the In This Issue feature, p. 1.

Published
2022

50. Multiomic Profiling of Central Nervous System Leukemia Identifies mRNA Translation as a Therapeutic Target

Author

Genetica Sectie Genoomdiagnostiek, Vanner, Robert J, Dobson, Stephanie M, Gan, Olga I, McLeod, Jessica, Schoof, Erwin M, Grandal, Ildiko, Wintersinger, Jeff A, Garcia-Prat, Laura, Hosseini, Mohsen, Xie, Stephanie Z, Jin, Liqing, Mbong, Nathan, Voisin, Veronique, Chan-Seng-Yue, Michelle, Kennedy, James A, Waanders, Esmé, Morris, Quaid, Porse, Bo, Chan, Steven M, Guidos, Cynthia J, Danska, Jayne S, Minden, Mark D, Mullighan, Charles G, Dick, John E, Genetica Sectie Genoomdiagnostiek, Vanner, Robert J, Dobson, Stephanie M, Gan, Olga I, McLeod, Jessica, Schoof, Erwin M, Grandal, Ildiko, Wintersinger, Jeff A, Garcia-Prat, Laura, Hosseini, Mohsen, Xie, Stephanie Z, Jin, Liqing, Mbong, Nathan, Voisin, Veronique, Chan-Seng-Yue, Michelle, Kennedy, James A, Waanders, Esmé, Morris, Quaid, Porse, Bo, Chan, Steven M, Guidos, Cynthia J, Danska, Jayne S, Minden, Mark D, Mullighan, Charles G, and Dick, John E

Published
2022

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