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1. The genomic basis of childhood T-lineage acute lymphoblastic leukaemia

Author

Pölönen, Petri, Di Giacomo, Danika, Seffernick, Anna Eames, Elsayed, Abdelrahman, Kimura, Shunsuke, Benini, Francesca, Montefiori, Lindsey E., Wood, Brent L., Xu, Jason, Chen, Changya, Cheng, Zhongshan, Newman, Haley, Myers, Jason, Iacobucci, Ilaria, Li, Elizabeth, Sussman, Jonathan, Hedges, Dale, Hui, Yawei, Diorio, Caroline, Uppuluri, Lahari, Frank, David, Fan, Yiping, Chang, Yunchao, Meshinchi, Soheil, Ries, Rhonda, Shraim, Rawan, Li, Alexander, Bernt, Kathrin M., Devidas, Meenakshi, Winter, Stuart S., Dunsmore, Kimberly P., Inaba, Hiroto, Carroll, William L., Ramirez, Nilsa C., Phillips, Aaron H., Kriwacki, Richard W., Yang, Jun J., Vincent, Tiffaney L., Zhao, Yaqi, Ghate, Pankaj S., Wang, Jian, Reilly, Colleen, Zhou, Xin, Sanders, Mathijs A., Takita, Junko, Kato, Motohiro, Takasugi, Nao, Chang, Bill H., Press, Richard D., Loh, Mignon, Rampersaud, Evadnie, Raetz, Elizabeth, Hunger, Stephen P., Tan, Kai, Chang, Ti-Cheng, Wu, Gang, Pounds, Stanley B., Mullighan, Charles G., and Teachey, David T.

Published
2024
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2. The St. Jude STEM Clubs: An Afterschool STEM Club for Upper Elementary School Students in Memphis, TN

Author

Ayers, Katherine A., Wade-Jaimes, Katherine, Wang, Lei, Pennella, Robyn A., and Pounds, Stanley B.

Abstract

Informal science, technology, engineering, and math (STEM) programs are important tools for broadening participation in STEM careers. The St. Jude STEM Club (SJSC) is a 10-week afterschool STEM club focused on real-world problems in pediatric cancer research and designed for students in the fifth grade. The SJSC is conducted in partnership with the Shelby County Schools (SCS), an urban school district that encompasses Memphis, TN and serves a disproportionate number of students from underrepresented backgrounds in science. In this report, we provide details on the club logistics, curriculum, pilot data and outcomes related to club impact on student attitudes towards science, and challenges and limitations of the program. Participants in the program reported significantly higher rates of STEM engagement, STEM identity, critical thinking, perseverance, and relationships with peers and adults compared to national normative data. This program description is intended to serve as a resource for other institutions wanting to use a similar strategy to broaden participation in STEM careers.

Published
2020

4. Genome-wide CRISPR/Cas9 screen identifies etoposide response modulators associated with clinical outcomes in pediatric AML

Author

Nguyen, Nam H. K., Rafiee, Roya, Tagmount, Abderrahmane, Sobh, Amin, Loguinov, Alex, de Jesus Sosa, Angelica K., Elsayed, Abdelrahman H., Gbadamosi, Mohammed, Seligson, Nathan, Cogle, Christopher R., Rubnitz, Jeffery, Ribeiro, Raul, Downing, James, Cao, Xueyuan, Pounds, Stanley B., Vulpe, Christopher D., and Lamba, Jatinder K.

Published
2023
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5. Genomic subtyping and therapeutic targeting of acute erythroleukemia

Author

Iacobucci, Ilaria, Wen, Ji, Meggendorfer, Manja, Choi, John K, Shi, Lei, Pounds, Stanley B, Carmichael, Catherine L, Masih, Katherine E, Morris, Sarah M, Lindsley, R Coleman, Janke, Laura J, Alexander, Thomas B, Song, Guangchun, Qu, Chunxu, Li, Yongjin, Payne-Turner, Debbie, Tomizawa, Daisuke, Kiyokawa, Nobutaka, Valentine, Marcus, Valentine, Virginia, Basso, Giuseppe, Locatelli, Franco, Enemark, Eric J, Kham, Shirley KY, Yeoh, Allen EJ, Ma, Xiaotu, Zhou, Xin, Sioson, Edgar, Rusch, Michael, Ries, Rhonda E, Stieglitz, Elliot, Hunger, Stephen P, Wei, Andrew H, To, L Bik, Lewis, Ian D, D’Andrea, Richard J, Kile, Benjamin T, Brown, Anna L, Scott, Hamish S, Hahn, Christopher N, Marlton, Paula, Pei, Deqing, Cheng, Cheng, Loh, Mignon L, Ebert, Benjamin L, Meshinchi, Soheil, Haferlach, Torsten, and Mullighan, Charles G

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Bioinformatics and Computational Biology, Genetics, Agricultural Biotechnology, Human Genome, Pediatric, Clinical Research, Rare Diseases, Pediatric Cancer, Orphan Drug, Hematology, Childhood Leukemia, Precision Medicine, Cancer, Biotechnology, Cancer Genomics, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Adolescent, Adult, Child, Child, Preschool, Female, Genomics, Homeodomain Proteins, Humans, Infant, Infant, Newborn, Leukemia, Erythroblastic, Acute, Male, Mutation, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, Nucleophosmin, Prognosis, Tumor Suppressor Protein p53, Young Adult, fms-Like Tyrosine Kinase 3, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Targetable signaling mutations were present in 45% of cases and included recurrent mutations of ALK and NTRK1, the latter of which drives erythroid leukemogenesis sensitive to TRK inhibition. This genomic landscape of AEL provides the framework for accurate diagnosis and risk stratification of this disease, and the rationale for testing targeted therapies in this high-risk leukemia.

Published
2019

8. Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor

Author

Murphy, Andrew J., Chen, Xiang, Pinto, Emilia M., Williams, Justin S., Clay, Michael R., Pounds, Stanley B., Cao, Xueyuan, Shi, Lei, Lin, Tong, Neale, Geoffrey, Morton, Christopher L., Woolard, Mary A., Mulder, Heather L., Gil, Hyea Jin, Rehg, Jerold E., Billups, Catherine A., Harlow, Matthew L., Dome, Jeffrey S., Houghton, Peter J., Easton, John, Zhang, Jinghui, George, Rani E., Zambetti, Gerard P., and Davidoff, Andrew M.

Published
2019
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9. The genomic landscape of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21

Author

Gao, Qingsong, primary, Ryan, Sarra L, additional, Iacobucci, Ilaria, additional, Ghate, Pankaj S, additional, Cranston, Ruth E, additional, Schwab, Claire J, additional, Elsayed, Abdelrahman H., additional, Shi, Lei, additional, Pounds, Stanley B, additional, Lei, Shaohua, additional, Baviskar, Pradyumna, additional, Pei, Deqing, additional, Cheng, Cheng, additional, Bashton, Matthew, additional, Sinclair, Paul B, additional, Bentley, David R, additional, Ross, Mark, additional, Kingsbury, Zoya, additional, James, Terena, additional, Roberts, Kathryn G, additional, Devidas, Meenakshi, additional, Fan, Yiping, additional, Chen, Wenan, additional, Chang, Ti-Cheng, additional, Wu, Gang, additional, Carroll, Andrew J., additional, Heerema, Nyla A., additional, Valentine, Virginia, additional, Valentine, Marcus B, additional, Yang, Wenjian, additional, Yang, Jun J., additional, Moorman, Anthony V, additional, Harrison, Christine J, additional, and Mullighan, Charles G., additional

Published
2023
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11. Single-Cell Pan-Cancer Analysis Reveals Treatment Resistance Stem/Progenitor-like Subpopulation in the High-Risk Pediatric Leukemia

Author

Chen, Changya, primary, Xu, Jason, additional, Vincent, Tiffaney L., additional, Yu, Wenbao, additional, Ding, Yang Y, additional, Chen, Chia-hui, additional, Kim, Samuel, additional, Li, Elizabeth, additional, Bandyopadhyay, Shovik, additional, Pölönen, Petri, additional, Elsayed, Abdelrahman, additional, Newman, Haley, additional, Wood, Brent L., additional, Hu, Jianzhong, additional, Shraim, Rawan, additional, Loh, Mignon L., additional, Raetz, Elizabeth A., additional, Hunger, Stephen P., additional, Pounds, Stanley B., additional, Yang, Jun J., additional, Mullighan, Charles G., additional, Frank, David, additional, Bernt, Kathrin M., additional, Teachey, David T., additional, and Tan, Kai, additional

Published
2022
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12. The Influence of Genetic Ancestry on Disease Biology in Pediatric T-Cell Acute Lymphoblastic Leukemia

Author

Newman, Haley, primary, Lee, Shawn, additional, Pölönen, Petri, additional, Shraim, Rawan, additional, Li, Yimei, additional, Liu, Hongyan, additional, Vincent, Tiffaney L., additional, Aplenc, Richard, additional, Chen, Changya, additional, Chen, Zhiguo, additional, Diorio, Caroline, additional, Dunsmore, Kimberly P., additional, Gupta, Sumit, additional, Wu, Gang, additional, Tan, Kai, additional, Devidas, Meenakshi, additional, Winter, Stuart S., additional, Wood, Brent L., additional, Winestone, Lena E., additional, Xu, Jason, additional, Raetz, Elizabeth A., additional, Loh, Mignon L., additional, Hunger, Stephen P., additional, Pounds, Stanley B., additional, Bona, Kira O, additional, Mullighan, Charles G., additional, Yang, Jun J., additional, and Teachey, David T., additional

Published
2022
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15. A Transcriptional Classifier Identifies Pediatric T-Cell Acute Lymphoblastic Leukemias at High Risk for End of Induction Minimal Residual Disease

Author

Meyer, Lauren K., primary, Roy, Ritu P., additional, Pölönen, Petri, additional, Elsayed, Abdelrahman, additional, Huang, Benjamin J., additional, Kimura, Shunsuke, additional, Delgado-Martin, Cristina, additional, Vincent, Tiffaney L., additional, Ryan, Theresa, additional, Wood, Brent L., additional, Chen, Zhiguo, additional, Liu, Yu, additional, Zhang, Jinghui, additional, Horton, Terzah M., additional, Loh, Mignon L., additional, Devidas, Meenakshi, additional, Raetz, Elizabeth A., additional, Hayashi, Robert J., additional, Winter, Stuart S., additional, Dunsmore, Kimberly P., additional, Hunger, Stephen P., additional, Pounds, Stanley B., additional, Hermiston, Michelle L., additional, Yang, Jun J., additional, Mullighan, Charles G., additional, Teachey, David T., additional, and Olshen, Adam B., additional

Published
2022
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16. Genome-Wide Association Study Identifies Variants Associated with Clinical Outcomes in Pediatric Patients with Newly Diagnosed Acute Myeloid Leukemia

Author

Marrero, Richard J, primary, Cao, Xueyuan, additional, Wu, Huiyun, additional, Inaba, Hiroto, additional, Raimondi, Susana C., additional, Pui, Ching-Hon, additional, Ribeiro, Raul C., additional, Rubnitz, Jeffrey E., additional, Pounds, Stanley B., additional, and Lamba, Jatinder K., additional

Published
2022
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17. Comprehensive Genome Characterization of Childhood T-ALL Links Oncogene Activation Mechanism and Subtypes to Prognosis

Author

Pölönen, Petri, primary, Elsayed, Abdelrahman, additional, Di Giacomo, Danika, additional, Montefiori, Lindsey, additional, Kimura, Shunsuke, additional, Myers, Jason, additional, Hedges, Dale, additional, Xu, Jason, additional, Hui, Yawei, additional, Cheng, Zhongshan, additional, Fan, Yiping, additional, Iacobucci, Ilaria, additional, Chang, Yunchao, additional, Shraim, Rawan, additional, Devidas, Meenakshi, additional, Winter, Stuart S., additional, Dunsmore, Kimberly P., additional, Yang, Jun J.J., additional, Vincent, Tiffaney L., additional, Tan, Kai, additional, Chen, Changya, additional, Newman, Haley, additional, Loh, Mignon L., additional, Raetz, Elizabeth A., additional, Hunger, Stephen P., additional, Rampersaud, Evadnie, additional, Chang, Ti-Cheng, additional, Wu, Gang, additional, Pounds, Stanley B., additional, Mullighan, Charles G., additional, and Teachey, David T., additional

Published
2022
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19. Personalization of Induction Therapy for Pediatric AML to Ara-C+Dauno+ Etoposide (ADE) or Clofarabine+Ara-C According to a Polygenic Ara-C SNP Score- ACS10

Author

Lamba, Jatinder K., primary, Marrero, Richard J, additional, Elsayed, Abdelrahman H, additional, Cao, Xueyuan, additional, Wu, Huiyun, additional, Inaba, Hiroto, additional, Raimondi, Susana C., additional, Pui, Ching-Hon, additional, Ribeiro, Raul C., additional, Rubnitz, Jeffrey E., additional, and Pounds, Stanley B., additional

Published
2022
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20. Progenitor Sub-Populations in Treatment Resistant T-ALL

Author

Xu, Jason, primary, Chen, Changya, additional, Vincent, Tiffaney L., additional, Pölönen, Petri, additional, Elsayed, Abdelrahman, additional, Hu, Jianzhong, additional, Yoshimura, Satoshi, additional, Yu, Wenbao, additional, Chen, Chia-hui, additional, Li, Elizabeth, additional, Shraim, Rawan, additional, Lavaert, Marieke, additional, Newman, Haley, additional, Ding, Yang-yang, additional, Thadi, Anusha, additional, Ahn, Kyung Jin, additional, Peng, Jacqueline, additional, Gong, Chujie, additional, Sun, Yusha, additional, Bandyopadhyay, Shovik, additional, Frank, David, additional, Loh, Mignon L., additional, Raetz, Elizabeth A., additional, Chen, Zhiguo, additional, Wood, Brent L., additional, Devidas, Meenakshi, additional, Dunsmore, Kimberly P., additional, Winter, Stuart S., additional, Wu, Gang, additional, Bhandoola, Avinash, additional, Pounds, Stanley B., additional, Hunger, Stephen P., additional, Yang, Jun J., additional, Mullighan, Charles G., additional, Teachey, David T., additional, and Tan, Kai, additional

Published
2022
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23. Genomic Analysis Reveals Few Genetic Alterations in Pediatrie Acute Myeloid Leukemia

Author

Radtke, Ina, Mullighan, Charles G., Ishii, Masami, Su, Xiaoping, Cheng, Jinjun, Ma, Jing, Ganti, Ramapriya, Cai, Zhongling, Goorha, Salii, Pounds, Stanley B., Cao, Xueyuan, Obert, Caroline, Armstrong, Jianling, Zhang, Jinghui, Song, Guangchun, Ribeiro, Raul C., Rubnitz, Jeffrey E., Raimondi, Susana C., Shurtleff, Sheila A., Downing, James R., and Rowley, Janet D.

Published
2009
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24. Integrated Genomic Analysis Identifies UBTF Tandem Duplications As a Subtype-Defining Lesion in Pediatric Acute Myeloid Leukemia

Author

Umeda, Masayuki, primary, Ma, Jing, additional, Huang, Benjamin J., additional, Hagiwara, Kohei, additional, Westover, Tamara, additional, Abdelhamed, Sherif, additional, Barajas, Juan Martin, additional, Thomas, Melvin Edward, additional, Walsh, Michael P, additional, Song, Guangchun, additional, Tian, Liqing, additional, Liu, Yanling, additional, Chen, Xiaolong, additional, Kolekar, Pandurang, additional, Tran, Quang, additional, Foy, Scott, additional, Maciaszek, Jamie L., additional, Kleist, Andrew B, additional, Leonti, Amanda R., additional, Ju, Bensheng, additional, Easton, John, additional, Wu, Huiyun, additional, Valentine, Virginia, additional, Valentine, Marc, additional, Liu, Yen-Chun, additional, Ries, Rhonda E., additional, Smith, Jenny L., additional, Parganas, Evan, additional, Iacobucci, Ilaria, additional, Hiltenbrand, Ryan, additional, Miller, Jonathan, additional, Myers, Jason, additional, Rampersaud, Evadnie, additional, Rahbarinia, Delaram, additional, Rusch, Michael, additional, Wu, Gang, additional, Inaba, Hiroto, additional, Wang, Yi-Cheng, additional, Alonzo, Todd A., additional, Downing, James R., additional, Mullighan, Charles G., additional, Pounds, Stanley B, additional, Babu, M. Madan, additional, Zhang, Jinghui, additional, Rubnitz, Jeffrey E., additional, Meshinchi, Soheil, additional, Ma, Xiaotu, additional, and Klco, Jeffery M., additional

Published
2021
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28. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia

Author

Mullighan, Charles G., Goorha, Salil, Radtke, Ina, Miller, Christopher B., Coustan-Smith, Elaine, Dalton, James D., Girtman, Kevin, Mathew, Susan, Ma, Jing, Pounds, Stanley B., Su, Xiaoping, Pui, Ching-Hon, Relling, Mary V., Evans, William E., Shurtleff, Sheila A., and Downing, James R.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Charles G. Mullighan [1, 6]; Salil Goorha [1, 6]; Ina Radtke [1]; Christopher B. Miller [1]; Elaine Coustan-Smith [2]; James D. Dalton [1]; Kevin Girtman [1]; Susan Mathew [1, [...]

Published
2007
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29. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

Author

Zhang, Jinghui, Ding, Li, Holmfeldt, Linda, Wu, Gang, Heatley, Sue L., Payne-Turner, Debbie, Easton, John, Chen, Xiang, Wang, Jianmin, Rusch, Michael, Lu, Charles, Chen, Shann-Ching, Wei, Lei, Collins-Underwood, Racquel J., Ma, Jing, Roberts, Kathryn G., Pounds, Stanley B., Ulyanov, Anatoly, Becksfort, Jared, Gupta, Pankaj, Huether, Robert, Kriwacki, Richard W., Parker, Matthew, McGoldrick, Daniel J., Zhao, David, Alford, Daniel, Espy, Stephen, Bobba, Kiran Chand, Song, Guangchun, Pei, Deqing, Cheng, Cheng, Roberts, Stefan, Barbato, Michael I., Campana, Dario, Coustan-Smith, Elaine, Shurtleff, Sheila A., Raimondi, Susana C., Kleppe, Maria, Cools, Jan, Shimano, Kristin A., Hermiston, Michelle L., Doulatov, Sergei, Eppert, Kolja, Laurenti, Elisa, Notta, Faiyaz, Dick, John E., Basso, Giuseppe, Hunger, Stephen P., Loh, Mignon L., Devidas, Meenakshi, Wood, Brent, Winter, Stuart, Dunsmore, Kimberley P., Fulton, Robert S., Fulton, Lucinda L., Hong, Xin, Harris, Christopher C., Dooling, David J., Ochoa, Kerri, Johnson, Kimberly J., Obenauer, John C., Evans, William E., Pui, Ching-Hon, Naeve, Clayton W., Ley, Timothy J., Mardis, Elaine R., Wilson, Richard K., Downing, James R., and Mullighan, Charles G.

Published
2012
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31. Sorafenib Population Pharmacokinetics and Skin Toxicities in Children and Adolescents with Refractory/Relapsed Leukemia or Solid Tumor Malignancies

Author

Inaba, Hiroto, primary, Panetta, John C., additional, Pounds, Stanley B., additional, Wang, Lei, additional, Li, Lie, additional, Navid, Fariba, additional, Federico, Sara M., additional, Eisenmann, Eric D., additional, Vasilyeva, Aksana, additional, Wang, Yong-Dong, additional, Shurtleff, Sheila, additional, Pui, Ching-Hon, additional, Gruber, Tanja A., additional, Ribeiro, Raul C., additional, Rubnitz, Jeffrey E., additional, and Baker, Sharyn D., additional

Published
2019
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32. Cross-species genomics matches driver mutations and cell compartments to model ependymoma

Author

Johnson, Robert A., Wright, Karen D., Poppleton, Helen, Mohankumar, Kumarasamypet M., Finkelstein, David, Pounds, Stanley B., Rand, Vikki, Leary, Sarah E. S., White, Elsie, Eden, Christopher, Hogg, Twala, Northcott, Paul, Mack, Stephen, Neale, Geoffrey, Wang, Yong-Dong, Coyle, Beth, Atkinson, Jennifer, DeWire, Mariko, Kranenburg, Tanya A., Gillespie, Yancey, Allen, Jeffrey C., Merchant, Thomas, Boop, Fredrick A., Sanford, Robert. A., Gajjar, Amar, Ellison, David W., Taylor, Michael D., Grundy, Richard G., and Gilbertson, Richard J.

Published
2010
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35. Uncovering the Genomic Landscape in Newly Diagnosed and Relapsed Pediatric Cytogenetically Normal FLT 3‐ ITD AML

Author

Buelow, Daelynn R., primary, Pounds, Stanley B., additional, Wang, Yong‐Dong, additional, Shi, Lei, additional, Li, Yongjin, additional, Finkelstein, David, additional, Shurtleff, Sheila, additional, Neale, Geoffrey, additional, Inaba, Hiroto, additional, Ribeiro, Raul C., additional, Palumbo, Reid, additional, Garrison, Dominique, additional, Orwick, Shelley J., additional, Blachly, James S., additional, Kroll, Karl, additional, Byrd, John C., additional, Gruber, Tanja A., additional, Rubnitz, Jeffrey E., additional, and Baker, Sharyn D., additional

Published
2019
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37. Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression

Author

Larson, Jon D., primary, Kasper, Lawryn H., additional, Paugh, Barbara S., additional, Jin, Hongjian, additional, Wu, Gang, additional, Kwon, Chang-Hyuk, additional, Fan, Yiping, additional, Shaw, Timothy I., additional, Silveira, André B., additional, Qu, Chunxu, additional, Xu, Raymond, additional, Zhu, Xiaoyan, additional, Zhang, Junyuan, additional, Russell, Helen R., additional, Peters, Jennifer L., additional, Finkelstein, David, additional, Xu, Beisi, additional, Lin, Tong, additional, Tinkle, Christopher L., additional, Patay, Zoltan, additional, Onar-Thomas, Arzu, additional, Pounds, Stanley B., additional, McKinnon, Peter J., additional, Ellison, David W., additional, Zhang, Jinghui, additional, and Baker, Suzanne J., additional

Published
2019
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38. DNA Methylation‐Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.

Author

Buelow, Daelynn R., Anderson, Jason T., Pounds, Stanley B., Shi, Lei, Lamba, Jatinder K., Hu, Shuiying, Gibson, Alice A., Goodwin, Emily A., Sparreboom, Alex, and Baker, Sharyn D.

Subjects
ACUTE myeloid leukemia, CYTARABINE, DNA, CHILD patients, EPIGENETICS
Abstract

Reduced expression of the uptake transporter, OCTN1 (SLC22A4), has been reported as a strong predictor of poor event‐free and overall survival in multiple cohorts of patients with acute myeloid leukemia (AML) receiving the cytidine nucleoside analog, cytarabine (Ara‐C). To further understand the mechanistic basis of interindividual variability in the functional expression of OCTN1 in AML, we hypothesized a mechanistic connection to DNA methylation‐based epigenetic repression of SLC22A4. We found increased basal SLC22A4 methylation was associated with decreased Ara‐C uptake in AML cell lines. Pre‐treatment with hypomethylating agents, 5‐azacytidine, or decitabine, restored SLC22A4 mRNA expression, increased cellular uptake of Ara‐C, and was associated with increased cellular sensitivity to Ara‐C compared with vehicle‐treated cells. Additionally, lower SLC22A4 methylation status was associated with distinct clinical advantages in both adult and pediatric patients with AML. These findings suggest a regulatory mechanism is involved in the interindividual variability in response to Ara‐C, and provides a basis for the integration of hypomethylating agents into Ara‐C‐based treatment regimens. [ABSTRACT FROM AUTHOR]

Published
2021
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43. OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues

Author

Drenberg, Christina D., primary, Gibson, Alice A., additional, Pounds, Stanley B., additional, Shi, Lei, additional, Rhinehart, Dena P., additional, Li, Lie, additional, Hu, Shuiying, additional, Du, Guoqing, additional, Nies, Anne T., additional, Schwab, Matthias, additional, Pabla, Navjotsingh, additional, Blum, William, additional, Gruber, Tanja A., additional, Baker, Sharyn D., additional, and Sparreboom, Alex, additional

Published
2017
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44. Uncovering the Genomic Landscape in Newly Diagnosed and Relapsed Pediatric Cytogenetically Normal FLT3‐ITD AML.

Author

Buelow, Daelynn R., Pounds, Stanley B., Wang, Yong‐Dong, Shi, Lei, Li, Yongjin, Finkelstein, David, Shurtleff, Sheila, Neale, Geoffrey, Inaba, Hiroto, Ribeiro, Raul C., Palumbo, Reid, Garrison, Dominique, Orwick, Shelley J., Blachly, James S., Kroll, Karl, Byrd, John C., Gruber, Tanja A., Rubnitz, Jeffrey E., and Baker, Sharyn D.

Subjects
*ACUTE myeloid leukemia, *CHIMERIC proteins, *PROTEIN-tyrosine kinases, *NUCLEOTIDE sequence, *NUCLEOPHOSMIN, *GENE frequency, *NUCLEOTIDE sequencing
Abstract

Fms‐like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations, common in pediatric acute myeloid leukemia (AML), associate with early relapse and poor prognosis. Past studies have suggested additional cooperative mutations are required for leukemogenesis in FLT3‐ITD+ AML. Using RNA sequencing and a next‐generation targeted gene panel, we broadly characterize the co‐occurring genomic alterations in pediatric cytogenetically normal (CN) FLT3‐ITD+ AML to gain a deeper understanding of the clonal patterns and heterogeneity at diagnosis and relapse. We show that chimeric transcripts were present in 21 of 34 (62%) of de novo samples, 2 (6%) of these samples included a rare reoccurring fusion partner BCL11B. At diagnosis, the median number of mutations other than FLT3 per patient was 1 (range 0–3), which involved 8 gene pathways; WT1 and NPM1 mutations were frequently observed (35% and 24%, respectively). Fusion transcripts and high variant allele frequency (VAF) mutants, which included WT1,NPM1,SMARCA2,RAD21, and TYK2, were retained from diagnosis to relapse. We did observe reduction in VAF of simple or single mutation clones, but VAFs were preserved or expanded in more complex clones with multiple mutations. Our data provide the first insight into the genomic complexity of pediatric CN FLT3‐ITD+ AML and could help stratify future targeted treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2019
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47. CC-PROMISE effectively integrates two forms of molecular data with multiple biologically related endpoints.

Author

Xueyuan Cao, Crews, Kristine R., Downing, James, Lamba, Jatinder, and Pounds, Stanley B.

Subjects
DATA analysis, MICROARRAY technology, STATISTICAL evidence (Law), CANONICAL correlation (Statistics), GENES
Abstract

Background: As new technologies allow investigators to collect multiple forms of molecular data (genomic, epigenomic, transcriptomic, etc) and multiple endpoints on a clinical trial cohort, it will become necessary to effectively integrate all these data in a way that reliably identifies biologically important genes. Methods: We introduce CC-PROMISE as an integrated data analysis method that combines components of canonical correlation (CC) and projection onto the most interesting evidence (PROMISE). For each gene, CC-PROMISE first uses CC to compute scores that represent the association of two forms of molecular data with each other. Next, these scores are substituted into PROMISE to evaluate the statistical evidence that the molecular data show a biologically meaningful relationship with the endpoints. Results: CC-PROMISE shows outstanding performance in simulation studies and an example application involving pediatric leukemia. In simulation studies, CC-PROMISE controls the type I error (misleading significance) rate very near the nominal level across 100 distinct null settings in which no molecular-endpoint association exists. Also, CC-PROMISE has better statistical power than three other methods that control type I error in 396 of 400 (99 %) alternative settings for which a molecular-endpoint association is present; the power advantage of CC-PROMISE exceeds 30 % in 127 of the 400 (32 %) alternative settings. These advantages of CC-PROMISE are also observed in an example application. Conclusion: CC-PROMISE very effectively identifies genes for which some form of molecular data shows a biologically meaningful association with multiple related endpoints. Availability: The R package CCPROMISE is currently available from www.stjuderesearch.org/site/depts/biostats/ software. [ABSTRACT FROM AUTHOR]

Published
2016
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48. Clinical Activity, Pharmacokinetics, and Pharmacodynamics of Sorafenib In Pediatric Acute Myeloid Leukemia.

Author

Inaba, Hiroto, primary, Rubnitz, Jeffrey E, additional, Coustan-Smith, Elaine, additional, Li, Lie, additional, Furmanski, Brian D, additional, Mascara, Gerard P, additional, Shurtleff, Sheila A, additional, Pounds, Stanley B, additional, Pui, Ching-Hon, additional, Ribeiro, Raul C, additional, Campana, Dario, additional, and Baker, Sharyn D, additional

Published
2010
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49. High-Resolution Genome-Wide Profiling of DNA Copy Number Abnormalities and Gene Resequencing in Pediatric Acute Myeloid Leukemia (AML).

Author

Radtke, Ina, primary, Mullighan, Charles G., additional, Ishii, Masami, additional, Ma, Jing, additional, Su, Xiaoping, additional, Goorha, Salil, additional, Ganti, Ramapriya, additional, Cai, Zhongling, additional, Phillips, Letha A., additional, Pounds, Stanley B., additional, Dalton, James, additional, Raimondi, Susana C., additional, Rubnitz, Jeffrey E., additional, Ribeiro, Raul C., additional, Shurtleff, Sheila A., additional, and Downing, James R., additional

Published
2007
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50. High Resolution Genomic Profiling Using Single Nucleotide Polymorphism Microarrays Identifies Multiple Novel Genomic Lesions in Pediatric Acute Lymphoblastic Leukemia.

Author

Mullighan, Charles G., primary, Goorha, Salil, primary, Radtke, Ina, primary, Dalton, James, primary, Ma, Jing, primary, Pounds, Stanley B., primary, Su, Xiaoping, primary, Pui, Ching-Hon, primary, Relling, Mary V., primary, Evans, William E., primary, and Downing, James R., primary

Published
2006
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