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1. Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study

Author

Rheingold, Susan R., Bhojwani, Deepa, Ji, Lingyun, Xu, Xinxin, Devidas, Meenakshi, Kairalla, John A., Shago, Mary, Heerema, Nyla A., Carroll, Andrew J., Breidenbach, Heather, Borowitz, Michael, Wood, Brent L., Angiolillo, Anne L., Asselin, Barbara L., Bowman, W. Paul, Brown, Patrick, Dreyer, ZoAnn E., Dunsmore, Kimberly P., Hilden, Joanne M., Larsen, Eric, Maloney, Kelly, Matloub, Yousif, Mattano, Leonard A., Winter, Stuart S., Gore, Lia, Winick, Naomi J., Carroll, William L., Hunger, Stephen P., Raetz, Elizabeth A., and Loh, Mignon L.

Published
2024
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3. Outcomes in patients with ETV6::RUNX1or high-hyperdiploid B-ALL treated in the St. Jude Total Therapy XV/XVI studies

Author

Purvis, Katelyn, Zhou, Yinmei, Karol, Seth E., Rubnitz, Jeffrey E., Ribeiro, Raul C., Lee, Shawn, Yang, Jun J., Bowman, W. Paul, Wang, Lu, Dixon, Stephanie B., Roberts, Kathryn G., Gao, Qingsong, Cheng, Cheng, Mullighan, Charles G., Jeha, Sima, Pui, Ching-Hon, and Inaba, Hiroto

Abstract

•Among NCI high-risk patients, 93% with ETV6::RUNX1and 54% with hyperdiploid B-ALL had excellent outcomes with low-intensity therapy.•NCI high-risk patients with hyperdiploid B-ALL and slow early MRD response had worse outcomes and, therefore, require new approaches.

Published
2025
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4. Germline genetic variation in ETV6 and risk of childhood acute lymphoblastic leukaemia: a systematic genetic study

Author

Moriyama, Takaya, Metzger, Monika L, Wu, Gang, Nishii, Rina, Qian, Maoxiang, Devidas, Meenakshi, Yang, Wenjian, Cheng, Cheng, Cao, Xueyuan, Quinn, Emily, Raimondi, Susana, Gastier-Foster, Julie M, Raetz, Elizabeth, Larsen, Eric, Martin, Paul L, Bowman, W Paul, Winick, Naomi, Komada, Yoshihiro, Wang, Shuoguo, Edmonson, Michael, Xu, Heng, Mardis, Elaine, Fulton, Robert, Pui, Ching-Hon, Mullighan, Charles, Evans, William E, Zhang, Jinghui, Hunger, Stephen P, Relling, Mary V, Nichols, Kim E, Loh, Mignon L, and Yang, Jun J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetic Testing, Hematology, Human Genome, Clinical Research, Cancer, Childhood Leukemia, Genetics, Pediatric Cancer, Rare Diseases, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Age Factors, Biomarkers, Tumor, Case-Control Studies, Child, Child, Preschool, Computational Biology, DNA Mutational Analysis, Databases, Genetic, Exome, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Karyotyping, Male, Phenotype, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-ets, Repressor Proteins, Risk Factors, Treatment Outcome, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundHereditary predisposition is rarely suspected for childhood acute lymphoblastic leukaemia (ALL). Recent reports of germline ETV6 variations associated with substantial familial clustering of haematological malignancies indicated that this gene is a potentially important genetic determinant for ALL susceptibility. Our aims in this study were to comprehensively identify ALL predisposition variants in ETV6 and to determine the extent to which they contributed to the overall risk of childhood ALL.MethodsWhole-exome sequencing of an index family with several cases of ALL was done to identify causal variants for ALL predisposition. Targeted sequencing of ETV6 was done in children from the Children's Oncology Group and St Jude Children's Research Hospital front-line ALL trials. Patients were included in this study on the basis of their enrolment in these clinical trials and the availability of germline DNA. ETV6 variant genotypes were compared with non-ALL controls to define ALL-related germline risk variants. ETV6 variant function was characterised bioinformatically and correlated with clinical and demographic features in children with ALL.FindingsWe identified a novel non-sense ETV6 variant (p.Arg359X) with a high penetrance in an index family. Subsequent targeted sequencing of ETV6 in 4405 childhood ALL cases identified 31 exonic variants (four non-sense, 21 missense, one splice site, and five frameshift variants) that were potentially related to ALL risk in 35 cases (1%). 15 (48%) of 31 ALL-related ETV6 variants clustered in the erythroblast transformation specific domain and were predicted to be highly deleterious. Children with ALL-related ETV6 variants were significantly older at leukaemia diagnosis than those without (10·2 years [IQR 5·3-13·8] vs 4·7 years [3·0-8·7]; p=0·017). The hyperdiploid leukaemia karyotype was highly over-represented in ALL cases harbouring germline ETV6 risk variants compared with the wild-type group (nine [64%] of 14 cases vs 538 [27%] of 2007 cases; p=0·0050).InterpretationOur findings indicated germline ETV6 variations as the basis of a novel genetic syndrome associated with predisposition to childhood ALL. The development of recommendations for clinical interventions and surveillance for individuals harbouring ALL-related ETV6 variants are needed.FundingUS National Institutes of Health and American Lebanese Syrian Associated Charities.

Published
2015

5. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children.

Author

Xu, Heng, Zhang, Hui, Yang, Wenjian, Yadav, Rachita, Morrison, Alanna C, Qian, Maoxiang, Devidas, Meenakshi, Liu, Yu, Perez-Andreu, Virginia, Zhao, Xujie, Gastier-Foster, Julie M, Lupo, Philip J, Neale, Geoff, Raetz, Elizabeth, Larsen, Eric, Bowman, W Paul, Carroll, William L, Winick, Naomi, Williams, Richard, Hansen, Torben, Holm, Jens-Christian, Mardis, Elaine, Fulton, Robert, Pui, Ching-Hon, Zhang, Jinghui, Mullighan, Charles G, Evans, William E, Hunger, Stephen P, Gupta, Ramneek, Schmiegelow, Kjeld, Loh, Mignon L, Relling, Mary V, and Yang, Jun J

Subjects
Hematopoietic Stem Cells, Animals, Humans, Mice, Genetic Predisposition to Disease, DNA-Binding Proteins, Transcription Factors, Case-Control Studies, Mutagenesis, Site-Directed, Genotype, Germ-Line Mutation, Mutation, Missense, Child, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p15, Ikaros Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genetic Variation, Genome-Wide Association Study, HEK293 Cells, Mutagenesis, Site-Directed, Mutation, Missense
Abstract

There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant in CDKN2A associated with the development of ALL at genome-wide significance (rs3731249, P=9.4 × 10(-23), odds ratio=2.23). Functional studies indicate that this hypomorphic variant results in reduced tumour suppressor function of p16(INK4A), increases the susceptibility to leukaemic transformation of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation on ALL risk, highlighting the important and complex roles of CDKN2A-CDKN2B tumour suppressors in leukaemogenesis.

Published
2015

6. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse.

Author

Perez-Andreu, Virginia, Roberts, Kathryn G, Harvey, Richard C, Yang, Wenjian, Cheng, Cheng, Pei, Deqing, Xu, Heng, Gastier-Foster, Julie, E, Shuyu, Lim, Joshua Yew-Suang, Chen, I-Ming, Fan, Yiping, Devidas, Meenakshi, Borowitz, Michael J, Smith, Colton, Neale, Geoffrey, Burchard, Esteban G, Torgerson, Dara G, Klussmann, Federico Antillon, Villagran, Cesar Rolando Najera, Winick, Naomi J, Camitta, Bruce M, Raetz, Elizabeth, Wood, Brent, Yue, Feng, Carroll, William L, Larsen, Eric, Bowman, W Paul, Loh, Mignon L, Dean, Michael, Bhojwani, Deepa, Pui, Ching-Hon, Evans, William E, Relling, Mary V, Hunger, Stephen P, Willman, Cheryl L, Mullighan, Charles G, and Yang, Jun J

Subjects
Humans, Genetic Predisposition to Disease, Recurrence, Risk, Case-Control Studies, Gene Frequency, Genotype, Inheritance Patterns, Polymorphism, Single Nucleotide, Child, GATA3 Transcription Factor, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Genome-Wide Association Study, Cancer, Childhood Leukemia, Rare Diseases, Pediatric, Hematology, Orphan Drug, Pediatric Research Initiative, Pediatric Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a high-risk subtype with an expression signature resembling that of Philadelphia chromosome-positive ALL and poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a susceptibility locus for Ph-like ALL (GATA3, rs3824662; P = 2.17 × 10(-14), odds ratio (OR) = 3.85 for Ph-like ALL versus non-ALL; P = 1.05 × 10(-8), OR = 3.25 for Ph-like ALL versus non-Ph-like ALL), with independent validation. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (CRLF2 rearrangement, JAK gene mutation and IKZF1 deletion) and with variation in GATA3 expression. Finally, genotype at the GATA3 SNP was also associated with early treatment response and risk of ALL relapse. Our results provide insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.

Published
2013

7. Novel Susceptibility Variants at 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethnically Diverse Populations

Author

Xu, Heng, Yang, Wenjian, Perez-Andreu, Virginia, Devidas, Meenakshi, Fan, Yiping, Cheng, Cheng, Pei, Deqing, Scheet, Paul, Burchard, Esteban González, Eng, Celeste, Huntsman, Scott, Torgerson, Dara G, Dean, Michael, Winick, Naomi J, Martin, Paul L, Camitta, Bruce M, Bowman, W Paul, Willman, Cheryl L, Carroll, William L, Mullighan, Charles G, Bhojwani, Deepa, Hunger, Stephen P, Pui, Ching-Hon, Evans, William E, Relling, Mary V, Loh, Mignon L, and Yang, Jun J

Subjects
Hematology, Rare Diseases, Cancer, Human Genome, Pediatric Cancer, Pediatric, Prevention, Childhood Leukemia, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adolescent, African Americans, CCAAT-Enhancer-Binding Proteins, Child, Child, Preschool, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 7, DNA-Binding Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Ikaros Transcription Factor, Logistic Models, Male, Mitogen-Activated Protein Kinase 7, Neoplasm Proteins, Phosphotransferases (Alcohol Group Acceptor), Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Risk Assessment, Risk Factors, Transcription Factors, Whites, White People, Black or African American, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundAcute lymphoblastic leukemia (ALL) is the most common cancer in children and the incidence of ALL varies by ethnicity. Although accumulating evidence indicates inherited predisposition to ALL, the genetic basis of ALL susceptibility in diverse ancestry has not been comprehensively examined.MethodsWe performed a multiethnic genome-wide association study in 1605 children with ALL and 6661 control subjects after adjusting for population structure, with validation in three replication series of 845 case subjects and 4316 control subjects. Association was tested by two-sided logistic regression.ResultsA novel ALL susceptibility locus at 10p12.31-12.2 (BMI1-PIP4K2A, rs7088318, P = 1.1 × 10(-11)) was identified in the genome-wide association study, with independent replication in European Americans, African Americans, and Hispanic Americans (P = .001, .009, and .04, respectively). Association was also validated at four known ALL susceptibility loci: ARID5B, IKZF1, CEBPE, and CDKN2A/2B. Associations at ARID5B, IKZF1, and BMI1-PIP4K2A variants were consistent across ethnicity, with multiple independent signals at IKZF1 and BMI1-PIP4K2A loci. The frequency of ARID5B and BMI1-PIP4K2A variants differed by ethnicity, in parallel with ethnic differences in ALL incidence. Suggestive evidence for modifying effects of age on genetic predisposition to ALL was also observed. ARID5B, IKZF1, CEBPE, and BMI1-PIP4K2A variants cumulatively conferred strong predisposition to ALL, with children carrying six to eight copies of risk alleles at a ninefold (95% confidence interval = 6.9 to 11.8) higher ALL risk relative to those carrying zero to one risk allele at these four single nucleotide polymorphisms.ConclusionsThese findings indicate strong associations between inherited genetic variation and ALL susceptibility in children and shed new light on ALL molecular etiology in diverse ancestry.

Published
2013

10. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity

Author

Fernandez, Christian A., Smith, Colton, Yang, Wenjian, Mullighan, Charles G., Qu, Chunxu, Larsen, Eric, Bowman, W. Paul, Liu, Chengcheng, Ramsey, Laura B., Chang, Tamara, Karol, Seth E., Loh, Mignon L., Raetz, Elizabeth A., Winick, Naomi J., Hunger, Stephen P., Carroll, William L., Jeha, Sima, Pui, Ching-Hon, Evans, William E., Devidas, Meenakshi, and Relling, Mary V.

Published
2015
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11. Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study

Author

Pui, Ching-Hon, Pei, Deqing, Coustan-Smith, Elaine, Jeha, Sima, Cheng, Cheng, Bowman, W Paul, Sandlund, John T, Ribeiro, Raul C, Rubnitz, Jeffrey E, Inaba, Hiroto, Bhojwani, Deepa, Gruber, Tanja A, Leung, Wing H, Downing, James R, Evans, William E, Relling, Mary V, and Campana, Dario

Published
2015
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13. Identification of TCF3 germline variants in pediatric B-cell acute lymphoblastic leukemia

Author

Escherich, Carolin S., primary, Chen, Wenan, additional, Miyamoto, Satoshi, additional, Namikawa, Yui, additional, Yang, Wenjian, additional, Teachey, David T., additional, Li, Zhenhua, additional, Raetz, Elizabeth A., additional, Larsen, Eric C., additional, Devidas, Meenakshi, additional, Martin, Paul L, additional, Bowman, W. Paul, additional, Wu, Gang, additional, Pui, Ching-Hon, additional, Hunger, Stephen P., additional, Loh, Mignon L., additional, Takagi, Masatoshi, additional, and Yang, Jun J., additional

Published
2022
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15. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies

Author

Fernandez, Christian A., Smith, Colton, Yang, Wenjian, Daté, Mihir, Bashford, Donald, Larsen, Eric, Bowman, W. Paul, Liu, Chengcheng, Ramsey, Laura B., Chang, Tamara, Turner, Victoria, Loh, Mignon L., Raetz, Elizabeth A., Winick, Naomi J., Hunger, Stephen P., Carroll, William L., Onengut-Gumuscu, Suna, Chen, Wei-Min, Concannon, Patrick, Rich, Stephen S., Scheet, Paul, Jeha, Sima, Pui, Ching-Hon, Evans, William E., Devidas, Meenakshi, and Relling, Mary V.

Published
2014
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17. Rare Deleterious TCF3 Germline Variants and Predisposition to Acute Lymphoblastic Leukemia in Children

Author

Escherich, Carolin, primary, Chen, Wenan, additional, Miyamoto, Satoshi, additional, Namikawa, Yui, additional, Yang, Wenjian, additional, Teachey, David T., additional, Li, Zhenhua, additional, Raetz, Elizabeth A., additional, Larsen, Eric C, additional, Devidas, Meenakshi, additional, Martin, Paul L., additional, Bowman, W Paul, additional, Wu, Gang, additional, Pui, Ching-Hon, additional, Hunger, Stephen P., additional, Takagi, Masatoshi, additional, Yang, Jun J., additional, and Loh, Mignon L., additional

Published
2022
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18. Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia

Author

Yang, Jun J., Cheng, Cheng, Devidas, Meenakshi, Cao, Xueyuan, Campana, Dario, Yang, Wenjian, Fan, Yiping, Neale, Geoff, Cox, Nancy, Scheet, Paul, Borowitz, Michael J., Winick, Naomi J., Martin, Paul L., Bowman, W. Paul, Camitta, Bruce, Reaman, Gregory H., Carroll, William L., Willman, Cheryl L., Hunger, Stephen P., Evans, William E., Pui, Ching-Hon, Loh, Mignon, and Relling, Mary V.

Published
2012
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19. Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group Study

Author

Chen, I-Ming, Harvey, Richard C., Mullighan, Charles G., Gastier-Foster, Julie, Wharton, Walker, Kang, Huining, Borowitz, Michael J., Camitta, Bruce M., Carroll, Andrew J., Devidas, Meenakshi, Pullen, D. Jeanette, Payne-Turner, Debbie, Tasian, Sarah K., Reshmi, Shalini, Cottrell, Catherine E., Reaman, Gregory H., Bowman, W. Paul, Carroll, William L., Loh, Mignon L., Winick, Naomi J., Hunger, Stephen P., and Willman, Cheryl L.

Published
2012
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21. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group

Author

Zhang, Jinghui, Mullighan, Charles G., Harvey, Richard C., Wu, Gang, Chen, Xiang, Edmonson, Michael, Buetow, Kenneth H., Carroll, William L., Chen, I-Ming, Devidas, Meenakshi, Gerhard, Daniela S., Loh, Mignon L., Reaman, Gregory H., Relling, Mary V., Camitta, Bruce M., Bowman, W. Paul, Smith, Malcolm A., Willman, Cheryl L., Downing, James R., and Hunger, Stephen P.

Published
2011
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22. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome

Author

Harvey, Richard C., Mullighan, Charles G., Wang, Xuefei, Dobbin, Kevin K., Davidson, George S., Bedrick, Edward J., Chen, I-Ming, Atlas, Susan R., Kang, Huining, Ar, Kerem, Wilson, Carla S., Wharton, Walker, Murphy, Maurice, Devidas, Meenakshi, Carroll, Andrew J., Borowitz, Michael J., Bowman, W. Paul, Downing, James R., Relling, Mary, Yang, Jun, Bhojwani, Deepa, Carroll, William L., Camitta, Bruce, Reaman, Gregory H., Smith, Malcolm, Hunger, Stephen P., and Willman, Cheryl L.

Published
2010
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23. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia

Author

Harvey, Richard C., Mullighan, Charles G., Chen, I-Ming, Wharton, Walker, Mikhail, Fady M., Carroll, Andrew J., Kang, Huining, Liu, Wei, Dobbin, Kevin K., Smith, Malcolm A., Carroll, William L., Devidas, Meenakshi, Bowman, W. Paul, Camitta, Bruce M., Reaman, Gregory H., Hunger, Stephen P., Downing, James R., and Willman, Cheryl L.

Published
2010
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24. Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia

Author

Kang, Huining, Chen, I.-Ming, Wilson, Carla S., Bedrick, Edward J., Harvey, Richard C., Atlas, Susan R., Devidas, Meenakshi, Mullighan, Charles G., Wang, Xuefei, Murphy, Maurice, Ar, Kerem, Wharton, Walker, Borowitz, Michael J., Bowman, W. Paul, Bhojwani, Deepa, Carroll, William L., Camitta, Bruce M., Reaman, Gregory H., Smith, Malcolm A., Downing, James R., Hunger, Stephen P., and Willman, Cheryl L.

Published
2010
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25. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial

Author

Rubnitz, Jeffrey E, Inaba, Hiroto, Dahl, Gary, Ribeiro, Raul C, Bowman, W Paul, Taub, Jeffrey, Pounds, Stanley, Razzouk, Bassem I, Lacayo, Norman J, Cao, Xueyuan, Meshinchi, Soheil, Degar, Barbara, Airewele, Gladstone, Raimondi, Susana C, Onciu, Mihaela, Coustan-Smith, Elaine, Downing, James R, Leung, Wing, Pui, Ching-Hon, and Campana, Dario

Published
2010
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29. Treating childhood acute lymphoblastic leukemia without cranial irradiation

Author

Pui, Ching-Hon, Campana, Dario, Pei, Deqing, Bowman, W. Paul, Sandlund, John T., Kaste, Sue C., Rubnitz, Jeffrey E., Raimondi, Susana C., Onciu, Mihaela, Ribeiro, Raul C., Coustan-Smith, Elaine, Kun, Larry E., Jeha, Sima, Cheng, Cheng, Howard, Scott C., Simmons, Vickey, Bayles, Amy, Metzger, Monika L., Boyett, James M., Leung, Wing, Handgretinger, Rupert, Downing, James R., Evans, William E., and Relling, Mary V.

Subjects
Acute lymphocytic leukemia -- Care and treatment, Chemotherapy -- Usage, Chemotherapy -- Health aspects, Cancer -- Chemotherapy, Cancer -- Usage, Cancer -- Health aspects
Abstract

A study was conducted to evaluate whether cranial irradiation could be excluded as a form of treatment among children with acute lymphoblastic leukemia (ALL). Results indicated that stopping such a form of treatment could be safely omitted with effective risk-adjusted chemotherapy.

Published
2009

30. Deletion on IKZF1 and prognosis in acute lymphoblastic leukemia

Author

Mullighan, Charles G., Xiaoping Su, Jinghui Zhang, Radtke, Ina, Phillips, Letha A.A., Miller, Christopher B., Jing Ma, Wei Liu, Cheng Cheng, Schulman, Brenda A., Harvey, Richard C., I-Ming Chen, Clifford, Robert J., Carroll, William L., Reaman, Gregory, Bowman, W. Paul, Devidas, Meenakshi, Gerhard, Daniela S., Wenjian Yang, Relling, Mary V., Shurtleff, Sheila A., Campana, Dario, Borowitz, Michael J., Ching-Hon Pui, Smith, Malcolm, Hunger, Stephen P., Willman, Cheryl L., and Downing, James R.

Subjects
Acute lymphocytic leukemia -- Risk factors, Acute lymphocytic leukemia -- Prognosis, Gene mutations -- Health aspects
Abstract

The study investigates children with high-risk B-cell-progenitor lymphoblastic leukemia (ALL), where copy-number abnormalities are identified as predictors of poor outcome based on deletion or mutation of IKZF1. Evidence suggests genetic alteration of IKZF1 is linked to very poor outcomes in B-cell-progenitor ALL.

Published
2009

32. Association ofGATA3Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia

Author

Zhang, Hui, primary, Liu, Anthony Pak-Yin, additional, Devidas, Meenakshi, additional, Lee, Shawn HR, additional, Cao, Xueyuan, additional, Pei, Deqing, additional, Borowitz, Michael, additional, Wood, Brent, additional, Gastier-Foster, Julie M, additional, Dai, Yunfeng, additional, Raetz, Elizabeth, additional, Larsen, Eric, additional, Winick, Naomi, additional, Bowman, W Paul, additional, Karol, Seth, additional, Yang, Wenjian, additional, Martin, Paul L, additional, Carroll, William L, additional, Pui, Ching-Hon, additional, Mullighan, Charles G, additional, Evans, William E, additional, Cheng, Cheng, additional, Hunger, Stephen P, additional, Relling, Mary V, additional, Loh, Mignon L, additional, and Yang, Jun J, additional

Published
2020
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34. Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics

Author

Qian, Maoxiang, Xu, Heng, Perez-Andreu, Virginia, Roberts, Kathryn G., Zhang, Hui, Yang, Wenjian, Zhang, Shouyue, Zhao, Xujie, Smith, Colton, Devidas, Meenakshi, Gastier-Foster, Julie M., Raetz, Elizabeth, Larsen, Eric, Burchard, Esteban G., Winick, Naomi, Bowman, W. Paul, Martin, Paul L., Borowitz, Michael, Wood, Brent, Antillon-Klussmann, Federico, Pui, Ching-Hon, Mullighan, Charles G., Evans, William E., Hunger, Stephen P., Relling, Mary V., Loh, Mignon L., and Yang, Jun J.

Published
2019
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36. Abstract 2881: Antiproliferative effect of copper complex of clotam in neuroblastoma cell lines

Author

Hernandez, Yazmin, primary, Grebennikov, Sarah Sarah, additional, Zakhary, Emily, additional, Dudhia, Ashni, additional, Maram, Rajasekhar, additional, Casanova, Diego, additional, Sankpal, Umesh T., additional, Bowman, W. Paul, additional, Brown, Deondra T., additional, Chhabra, Jaya, additional, Holder, Alvin A., additional, and Basha, Riyaz M., additional

Published
2019
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38. Educational attainment in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

Author

Bashore, Lisa, primary, Merchant, Zahra, additional, Lupo, Philip, additional, King, Allison A., additional, Hamby, Tyler, additional, Srivastava, Deokumar, additional, Howell, Rebecca M., additional, Gibson, Todd M., additional, Oeffinger, Kevin C., additional, Armstrong, Gregory T., additional, Bowman, W. Paul, additional, and Krull, Kevin R., additional

Published
2019
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40. Association of GATA3 Polymorphisms With Minimal Residual Disease and Relapse Risk in Childhood Acute Lymphoblastic Leukemia.

Author

Zhang, Hui, Liu, Anthony Pak-Yin, Devidas, Meenakshi, Lee, Shawn HR, Cao, Xueyuan, Pei, Deqing, Borowitz, Michael, Wood, Brent, Gastier-Foster, Julie M, Dai, Yunfeng, Raetz, Elizabeth, Larsen, Eric, Winick, Naomi, Bowman, W Paul, Karol, Seth, Yang, Wenjian, Martin, Paul L, Carroll, William L, Pui, Ching-Hon, and Mullighan, Charles G

Subjects
LYMPHOBLASTIC leukemia, ACUTE leukemia, PROGNOSIS, DISEASE relapse, LEUKOCYTE count, PROTEINS, POPULATION, RELATIVE medical risk, RESEARCH, CONFIDENCE intervals, SEQUENCE analysis, MULTIVARIATE analysis, CARCINOGENESIS, RESEARCH methodology, GENETIC polymorphisms, ALLELES, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, GENOTYPES, RESEARCH funding, ODDS ratio
Abstract

Background: Minimal residual disease (MRD) after induction therapy is one of the strongest prognostic factors in childhood acute lymphoblastic leukemia (ALL), and MRD-directed treatment intensification improves survival. Little is known about the effects of inherited genetic variants on interpatient variability in MRD.Methods: A genome-wide association study was performed on 2597 children on the Children's Oncology Group AALL0232 trial for high-risk B-cell ALL. Association between genotype and end-of-induction MRD levels was evaluated for 863 370 single nucleotide polymorphisms (SNPs), adjusting for genetic ancestry and treatment strata. Top variants were further evaluated in a validation cohort of 491 patients from the Children's Oncology Group P9905 and 6 ALL trials. The independent prognostic value of single nucleotide polymorphisms was determined in multivariable analyses. All statistical tests were 2-sided.Results: In the discovery genome-wide association study, we identified a genome-wide significant association at the GATA3 locus (rs3824662, odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.35 to 1.84; P = 1.15 × 10-8 as a dichotomous variable). This association was replicated in the validation cohort (P = .003, MRD as a dichotomous variable). The rs3824662 risk allele independently predicted ALL relapse after adjusting for age, white blood cell count, and leukemia DNA index (P = .04 and .007 in the discovery and validation cohort, respectively) and remained prognostic when the analyses were restricted to MRD-negative patients (P = .04 and .03 for the discovery and validation cohorts, respectively).Conclusion: Inherited GATA3 variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. This work highlights the potential utility of germline variants in upfront risk stratification in ALL. [ABSTRACT FROM AUTHOR]

Published
2021
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45. Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia

Author

Churchman, Michelle L., primary, Qian, Maoxiang, additional, te Kronnie, Geertruy, additional, Zhang, Ranran, additional, Yang, Wenjian, additional, Zhang, Hui, additional, Lana, Tobia, additional, Tedrick, Paige, additional, Baskin, Rebekah, additional, Verbist, Katherine, additional, Peters, Jennifer L., additional, Devidas, Meenakshi, additional, Larsen, Eric, additional, Moore, Ian M., additional, Gu, Zhaohui, additional, Qu, Chunxu, additional, Yoshihara, Hiroki, additional, Porter, Shaina N., additional, Pruett-Miller, Shondra M., additional, Wu, Gang, additional, Raetz, Elizabeth, additional, Martin, Paul L., additional, Bowman, W. Paul, additional, Winick, Naomi, additional, Mardis, Elaine, additional, Fulton, Robert, additional, Stanulla, Martin, additional, Evans, William E., additional, Relling, Mary V., additional, Pui, Ching-Hon, additional, Hunger, Stephen P., additional, Loh, Mignon L., additional, Handgretinger, Rupert, additional, Nichols, Kim E., additional, Yang, Jun J., additional, and Mullighan, Charles G., additional

Published
2018
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46. Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels

Author

Mullighan, Charles G., Jeha, Sima, Pei, Deqing, Payne-Turner, Debbie, Coustan-Smith, Elaine, Roberts, Kathryn G., Waanders, Esmé, Choi, John K., Ma, Xiaotu, Raimondi, Susana C., Fan, Yiping, Yang, Wenjian, Song, Guangchun, Yang, Jun J., Inaba, Hiroto, Downing, James R., Leung, Wing H., Bowman, W. Paul, Relling, Mary V., Evans, William E., Zhang, Jinghui, Campana, Dario, and Pui, Ching-Hon

Published
2015
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47. TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children

Author

Qian, Maoxiang, primary, Cao, Xueyuan, additional, Devidas, Meenakshi, additional, Yang, Wenjian, additional, Cheng, Cheng, additional, Dai, Yunfeng, additional, Carroll, Andrew, additional, Heerema, Nyla A., additional, Zhang, Hui, additional, Moriyama, Takaya, additional, Gastier-Foster, Julie M., additional, Xu, Heng, additional, Raetz, Elizabeth, additional, Larsen, Eric, additional, Winick, Naomi, additional, Bowman, W. Paul, additional, Martin, Paul L., additional, Mardis, Elaine R., additional, Fulton, Robert, additional, Zambetti, Gerard, additional, Borowitz, Michael, additional, Wood, Brent, additional, Nichols, Kim E., additional, Carroll, William L., additional, Pui, Ching-Hon, additional, Mullighan, Charles G., additional, Evans, William E., additional, Hunger, Stephen P., additional, Relling, Mary V., additional, Loh, Mignon L., additional, and Yang, Jun J., additional

Published
2018
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