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1. Integrated genomic analysis identifies UBTF tandem duplications as a recurrent lesion in pediatric acute myeloid leukemiaUBTF tandem duplications in pediatric acute myeloid leukemia

Author

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

Subjects
Pediatric Cancer, Pediatric Research Initiative, Clinical Research, Rare Diseases, Cancer, Genetics, Childhood Leukemia, Hematology, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Adult, Child, Chromosome Aberrations, Exons, Genomics, Humans, Leukemia, Myeloid, Acute, Mutation, Recurrence
Abstract

The genetics of relapsed pediatric acute myeloid leukemia (AML) has yet to be comprehensively defined. Here, we present the spectrum of genomic alterations in 136 relapsed pediatric AMLs. We identified recurrent exon 13 tandem duplications (TD) in upstream binding transcription factor (UBTF) in 9% of relapsed AML cases. UBTF-TD AMLs commonly have normal karyotype or trisomy 8 with cooccurring WT1 mutations or FLT3-ITD but not other known oncogenic fusions. These UBTF-TD events are stable during disease progression and are present in the founding clone. In addition, we observed that UBTF-TD AMLs account for approximately 4% of all de novo pediatric AMLs, are less common in adults, and are associated with poor outcomes and MRD positivity. Expression of UBTF-TD in primary hematopoietic cells is sufficient to enhance serial clonogenic activity and to drive a similar transcriptional program to UBTF-TD AMLs. Collectively, these clinical, genomic, and functional data establish UBTF-TD as a new recurrent mutation in AML.SignificanceWe defined the spectrum of mutations in relapsed pediatric AML and identified UBTF-TDs as a new recurrent genetic alteration. These duplications are more common in children and define a group of AMLs with intermediate-risk cytogenetic abnormalities, FLT3-ITD and WT1 alterations, and are associated with poor outcomes. See related commentary by Hasserjian and Nardi, p. 173. This article is highlighted in the In This Issue feature, p. 171.

Published
2022

2. 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

3. The genomic landscape of pediatric acute lymphoblastic leukemia

Author

Brady, Samuel W., Roberts, Kathryn G., Gu, Zhaohui, Shi, Lei, Pounds, Stanley, Pei, Deqing, Cheng, Cheng, Dai, Yunfeng, Devidas, Meenakshi, Qu, Chunxu, Hill, Ashley N., Payne-Turner, Debbie, Ma, Xiaotu, Iacobucci, Ilaria, Baviskar, Pradyuamna, Wei, Lei, Arunachalam, Sasi, Hagiwara, Kohei, Liu, Yanling, Flasch, Diane A., Liu, Yu, Parker, Matthew, Chen, Xiaolong, Elsayed, Abdelrahman H., Pathak, Omkar, Li, Yongjin, Fan, Yiping, Michael, J. Robert, Rusch, Michael, Wilkinson, Mark R., Foy, Scott, Hedges, Dale J., Newman, Scott, Zhou, Xin, Wang, Jian, Reilly, Colleen, Sioson, Edgar, Rice, Stephen V., Pastor Loyola, Victor, Wu, Gang, Rampersaud, Evadnie, Reshmi, Shalini C., Gastier-Foster, Julie, Guidry Auvil, Jaime M., Gesuwan, Patee, Smith, Malcolm A., Winick, Naomi, Carroll, Andrew J., Heerema, Nyla A., Harvey, Richard C., Willman, Cheryl L., Larsen, Eric, Raetz, Elizabeth A., Borowitz, Michael J., Wood, Brent L., Carroll, William L., Zweidler-McKay, Patrick A., Rabin, Karen R., Mattano, Leonard A., Maloney, Kelly W., Winter, Stuart S., Burke, Michael J., Salzer, Wanda, Dunsmore, Kimberly P., Angiolillo, Anne L., Crews, Kristine R., Downing, James R., Jeha, Sima, Pui, Ching-Hon, Evans, William E., Yang, Jun J., Relling, Mary V., Gerhard, Daniela S., Loh, Mignon L., Hunger, Stephen P., Zhang, Jinghui, and Mullighan, Charles G.

Published
2022
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5. Convergent genetic aberrations in murine and human T lineage acute lymphoblastic leukemias

Author

Huang, Benjamin J, Wandler, Anica M, Meyer, Lauren K, Dail, Monique, Daemen, Anneleen, Sampath, Deepak, Li, Qing, Wang, Xinyue, Wong, Jasmine C, Nakitandwe, Joy, Downing, James R, Zhang, Jinghui, Taylor, Barry S, and Shannon, Kevin

Subjects
Biological Sciences, Genetics, Human Genome, Orphan Drug, Pediatric Cancer, Rare Diseases, Pediatric, Hematology, Biotechnology, Cancer, Childhood Leukemia, 5.1 Pharmaceuticals, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Animals, Cell Line, Tumor, Chromosome Aberrations, Clonal Evolution, Disease Models, Animal, Drug Resistance, Neoplasm, Genomics, Humans, Mice, Mutagenesis, Insertional, Mutation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins p21(ras), Developmental Biology
Abstract

The lack of predictive preclinical models is a fundamental barrier to translating knowledge about the molecular pathogenesis of cancer into improved therapies. Insertional mutagenesis (IM) in mice is a robust strategy for generating malignancies that recapitulate the extensive inter- and intra-tumoral genetic heterogeneity found in advanced human cancers. While the central role of "driver" viral insertions in IM models that aberrantly increase the expression of proto-oncogenes or disrupt tumor suppressors has been appreciated for many years, the contributions of cooperating somatic mutations and large chromosomal alterations to tumorigenesis are largely unknown. Integrated genomic studies of T lineage acute lymphoblastic leukemias (T-ALLs) generated by IM in wild-type (WT) and Kras mutant mice reveal frequent point mutations and other recurrent non-insertional genetic alterations that also occur in human T-ALL. These somatic mutations are sensitive and specific markers for defining clonal dynamics and identifying candidate resistance mechanisms in leukemias that relapse after an initial therapeutic response. Primary cancers initiated by IM and resistant clones that emerge during in vivo treatment close key gaps in existing preclinical models, and are robust platforms for investigating the efficacy of new therapies and for elucidating how drug exposure shapes tumor evolution and patterns of resistance.

Published
2019

6. Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes

Author

Wong, Jasmine C, Bryant, Victoria, Lamprecht, Tamara, Ma, Jing, Walsh, Michael, Schwartz, Jason, del pilar Alzamora, Maria, Mullighan, Charles G, Loh, Mignon L, Ribeiro, Raul, Downing, James R, Carroll, William L, Davis, Jeffrey, Gold, Stuart, Rogers, Paul C, Israels, Sara, Yanofsky, Rochelle, Shannon, Kevin, and Klco, Jeffery M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Pediatric, Childhood Leukemia, Cancer, Rare Diseases, Hematology, Pediatric Cancer, Clinical Research, 2.1 Biological and endogenous factors, Cell Cycle, Chromosome Deletion, Chromosome Disorders, Chromosomes, Human, Pair 7, Disease Progression, Evolution, Molecular, Female, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Germ-Line Mutation, Hematologic Neoplasms, Humans, Intracellular Signaling Peptides and Proteins, Leukemia, Myeloid, Acute, Male, Myelodysplastic Syndromes, Neoplasms, Pedigree, Proteins, Tumor Suppressor Proteins, Leukemias, Biomedical and clinical sciences, Health sciences
Abstract

Germline SAMD9 and SAMD9L mutations cause a spectrum of multisystem disorders that carry a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Here, we describe 16 siblings, the majority of which were phenotypically normal, from 5 families diagnosed with myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7; OMIM 252270) who primarily had onset of hematologic abnormalities during the first decade of life. Molecular analyses uncovered germline SAMD9L (n = 4) or SAMD9 (n = 1) mutations in these families. Affected individuals had a highly variable clinical course that ranged from mild and transient dyspoietic changes in the bone marrow to a rapid progression of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7. Expression of these gain-of-function SAMD9 and SAMD9L mutations reduces cell cycle progression, and deep sequencing demonstrated selective pressure favoring the outgrowth of clones that have either lost the mutant allele or acquired revertant mutations. The myeloid malignancies of affected siblings acquired cooperating mutations in genes that are also altered in sporadic cases of AML characterized by monosomy 7. These data have implications for understanding how SAMD9 and SAMD9L mutations contribute to myeloid transformation and for recognizing, counseling, and treating affected families.

Published
2018

7. A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease

Author

Rampersaud, Evadnie, Kang, Guolian, Palmer, Lance E., Rashkin, Sara R., Wang, Shuoguo, Bi, Wenjian, Alberts, Nicole M., Anghelescu, Doralina, Barton, Martha, Birch, Kirby, Boulos, Nidal, Brandow, Amanda M., Brooke, Russell John, Chang, Ti-Cheng, Chen, Wenan, Cheng, Yong, Ding, Juan, Easton, John, Hodges, Jason R., Kanne, Celeste K., Levy, Shawn, Mulder, Heather, Patel, Ashwin P., Puri, Latika, Rosencrance, Celeste, Rusch, Michael, Sapkota, Yadav, Sioson, Edgar, Sharma, Akshay, Tang, Xing, Thrasher, Andrew, Wang, Winfred, Yao, Yu, Yasui, Yutaka, Yergeau, Donald, Hankins, Jane S., Sheehan, Vivien A., Downing, James R., Estepp, Jeremie H., Zhang, Jinghui, DeBaun, Michael, Wu, Gang, and Weiss, Mitchell J.

Published
2021
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8. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology

Author

Qaddoumi, Ibrahim, Orisme, Wilda, Wen, Ji, Santiago, Teresa, Gupta, Kirti, Dalton, James D, Tang, Bo, Haupfear, Kelly, Punchihewa, Chandanamali, Easton, John, Mulder, Heather, Boggs, Kristy, Shao, Ying, Rusch, Michael, Becksfort, Jared, Gupta, Pankaj, Wang, Shuoguo, Lee, Ryan P, Brat, Daniel, Peter Collins, V, Dahiya, Sonika, George, David, Konomos, William, Kurian, Kathreena M, McFadden, Kathryn, Serafini, Luciano Neder, Nickols, Hilary, Perry, Arie, Shurtleff, Sheila, Gajjar, Amar, Boop, Fredrick A, Klimo, Paul D, Mardis, Elaine R, Wilson, Richard K, Baker, Suzanne J, Zhang, Jinghui, Wu, Gang, Downing, James R, Tatevossian, Ruth G, and Ellison, David W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Genetics, Brain Cancer, Biotechnology, Brain Disorders, Rare Diseases, Neurosciences, Cancer, Adolescent, Adult, Astrocytoma, Brain Neoplasms, Child, Child, Preschool, DNA-Binding Proteins, Female, Ganglioglioma, Genes, myb, Genetic Predisposition to Disease, Glioma, Humans, Infant, Male, Mutation, Nuclear Proteins, Nucleocytoplasmic Transport Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, RNA-Binding Proteins, Receptor, Fibroblast Growth Factor, Type 1, Trans-Activators, Transcription Factors, Young Adult, Glioneuronal, RNA-seq, FGFR1, MYB, BRAF, Neurology & Neurosurgery
Abstract

Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials.

Published
2016

9. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia

Author

Li, Benshang, Brady, Samuel W., Ma, Xiaotu, Shen, Shuhong, Zhang, Yingchi, Li, Yongjin, Szlachta, Karol, Dong, Li, Liu, Yu, Yang, Fan, Wang, Ningling, Flasch, Diane A., Myers, Matthew A., Mulder, Heather L., Ding, Lixia, Liu, Yanling, Tian, Liqing, Hagiwara, Kohei, Xu, Ke, Zhou, Xin, Sioson, Edgar, Wang, Tianyi, Yang, Liu, Zhao, Jie, Zhang, Hui, Shao, Ying, Sun, Hongye, Sun, Lele, Cai, Jiaoyang, Sun, Hui-Ying, Lin, Ting-Nien, Du, Lijuan, Li, Hui, Rusch, Michael, Edmonson, Michael N., Easton, John, Zhu, Xiaofan, Zhang, Jingliao, Cheng, Cheng, Raphael, Benjamin J., Tang, Jingyan, Downing, James R., Alexandrov, Ludmil B., Zhou, Bin-Bing S., Pui, Ching-Hon, Yang, Jun J., and Zhang, Jinghui

Published
2020
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10. Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia.

Author

Iacobucci, Ilaria, Li, Yongjin, Roberts, Kathryn G, Dobson, Stephanie M, Kim, Jaeseung C, Payne-Turner, Debbie, Harvey, Richard C, Valentine, Marcus, McCastlain, Kelly, Easton, John, Yergeau, Donald, Janke, Laura J, Shao, Ying, Chen, I-Ming L, Rusch, Michael, Zandi, Sasan, Kornblau, Steven M, Konopleva, Marina, Jabbour, Elias, Paietta, Elisabeth M, Rowe, Jacob M, Pui, Ching-Hon, Gastier-Foster, Julie, Gu, Zhaohui, Reshmi, Shalini, Loh, Mignon L, Racevskis, Janis, Tallman, Martin S, Wiernik, Peter H, Litzow, Mark R, Willman, Cheryl L, McPherson, John D, Downing, James R, Zhang, Jinghui, Dick, John E, Hunger, Stephen P, and Mullighan, Charles G

Subjects
Humans, Receptors, Erythropoietin, Antineoplastic Agents, Amino Acid Sequence, Base Sequence, Gene Order, Mutation, Molecular Sequence Data, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Rare Diseases, Pediatric Cancer, Childhood Leukemia, Hematology, Pediatric, Stem Cell Research, Cancer, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL.

Published
2016

11. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia.

Author

Ma, Xiaotu, Edmonson, Michael, Yergeau, Donald, Muzny, Donna M, Hampton, Oliver A, Rusch, Michael, Song, Guangchun, Easton, John, Harvey, Richard C, Wheeler, David A, Ma, Jing, Doddapaneni, HarshaVardhan, Vadodaria, Bhavin, Wu, Gang, Nagahawatte, Panduka, Carroll, William L, Chen, I-Ming, Gastier-Foster, Julie M, Relling, Mary V, Smith, Malcolm A, Devidas, Meenakshi, Guidry Auvil, Jaime M, Downing, James R, Loh, Mignon L, Willman, Cheryl L, Gerhard, Daniela S, Mullighan, Charles G, Hunger, Stephen P, and Zhang, Jinghui

Subjects
Clone Cells, Humans, Neoplasm Recurrence, Local, Disease Progression, GTP Phosphohydrolases, 5'-Nucleotidase, Histone-Lysine N-Methyltransferase, Membrane Proteins, Extracellular Matrix Proteins, Repressor Proteins, Mutation, Child, Female, Male, Tumor Suppressor Protein p53, CREB-Binding Protein, Ikaros Transcription Factor, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, DNA Copy Number Variations, Exome, Clonal Evolution, Neoplasm Recurrence, Local, 5-Nucleotidase
Abstract

There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse.

Published
2015

12. Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL)

Author

Shaw, Timothy I., Dong, Li, Tian, Liqing, Qian, Chenxi, Liu, Yu, Ju, Bensheng, High, Anthony, Kavdia, Kanisha, Pagala, Vishwajeeth R., Shaner, Bridget, Pei, Deqing, Easton, John, Janke, Laura J., Porter, Shaina N., Ma, Xiaotu, Cheng, Cheng, Pruett-Miller, Shondra M., Choi, John, Yu, Jiyang, Peng, Junmin, Gu, Wei, Look, A. Thomas, Downing, James R., and Zhang, Jinghui

Published
2021
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13. Loss of oncogenic Notch1 with resistance to a PI3K inhibitor in T-cell leukaemia

Author

Dail, Monique, Wong, Jason, Lawrence, Jessica, O’Connor, Daniel, Nakitandwe, Joy, Chen, Shann-Ching, Xu, Jin, Lee, Leslie B, Akagi, Keiko, Li, Qing, Aster, Jon C, Pear, Warren S, Downing, James R, Sampath, Deepak, and Shannon, Kevin

Subjects
Pediatric, Cancer, Rare Diseases, Pediatric Cancer, Childhood Leukemia, Hematology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Benzamides, Clone Cells, Diphenylamine, Down-Regulation, Drug Resistance, Neoplasm, Drug Synergism, Genes, ras, Indazoles, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase Kinases, Phosphoinositide-3 Kinase Inhibitors, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Protein Kinase Inhibitors, Protein Structure, Tertiary, Proto-Oncogene Proteins c-akt, Receptor, Notch1, Signal Transduction, Sulfonamides, General Science & Technology
Abstract

Mutations that deregulate Notch1 and Ras/phosphoinositide 3 kinase (PI3K)/Akt signalling are prevalent in T-cell acute lymphoblastic leukaemia (T-ALL), and often coexist. Here we show that the PI3K inhibitor GDC-0941 is active against primary T-ALLs from wild-type and Kras(G12D) mice, and addition of the MEK inhibitor PD0325901 increases its efficacy. Mice invariably relapsed after treatment with drug-resistant clones, most of which unexpectedly had reduced levels of activated Notch1 protein, downregulated many Notch1 target genes, and exhibited cross-resistance to γ-secretase inhibitors. Multiple resistant primary T-ALLs that emerged in vivo did not contain somatic Notch1 mutations present in the parental leukaemia. Importantly, resistant clones upregulated PI3K signalling. Consistent with these data, inhibiting Notch1 activated the PI3K pathway, providing a likely mechanism for selection against oncogenic Notch1 signalling. These studies validate PI3K as a therapeutic target in T-ALL and raise the unexpected possibility that dual inhibition of PI3K and Notch1 signalling could promote drug resistance in T-ALL.

Published
2014

14. Runx1 exon 6–related alternative splicing isoforms differentially regulate hematopoiesis in mice

Author

Komeno, Yukiko, Yan, Ming, Matsuura, Shinobu, Lam, Kentson, Lo, Miao-Chia, Huang, Yi-Jou, Tenen, Daniel G, Downing, James R, and Zhang, Dong-Er

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Hematology, Stem Cell Research, Genetics, 2.1 Biological and endogenous factors, Animals, Base Sequence, Cells, Cultured, Core Binding Factor Alpha 2 Subunit, Exons, Gene Expression Regulation, HEK293 Cells, Hematopoiesis, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Protein Isoforms, RNA Splice Sites, Sequence Homology, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology, Biochemistry and cell biology, Cardiovascular medicine and haematology, Paediatrics
Abstract

RUNX1 is an important transcription factor for hematopoiesis. There are multiple alternatively spliced isoforms of RUNX1. The best known isoforms are RUNX1a from use of exon 7A and RUNX1b and c from use of exon 7B. RUNX1a has unique functions due to its lack of C-terminal regions common to RUNX1b and c. Here, we report that the ortholog of human RUNX1a was only found in primates. Furthermore, we characterized 3 Runx1 isoforms generated by exon 6 alternative splicing. Runx1bEx6(-) (Runx1b without exon 6) and a unique mouse Runx1bEx6e showed higher colony-forming activity than the full-length Runx1b (Runx1bEx6(+)). They also facilitated the transactivation of Runx1bEx6(+). To gain insight into in vivo functions, we analyzed a knock-in (KI) mouse model that lacks isoforms Runx1b/cEx6(-) and Runx1bEx6e. KI mice had significantly fewer lineage-Sca1(+)c-Kit(+) cells, short-term hematopoietic stem cells (HSCs) and multipotent progenitors than controls. In vivo competitive repopulation assays demonstrated a sevenfold difference of functional HSCs between wild-type and KI mice. Together, our results show that Runx1 isoforms involving exon 6 support high self-renewal capacity in vitro, and their loss results in reduction of the HSC pool in vivo, which underscore the importance of fine-tuning RNA splicing in hematopoiesis.

Published
2014

15. Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses

Author

Stewart, Elizabeth, McEvoy, Justina, Wang, Hong, Chen, Xiang, Honnell, Victoria, Ocarz, Monica, Gordon, Brittney, Dapper, Jason, Blankenship, Kaley, Yang, Yanling, Li, Yuxin, Shaw, Timothy I., Cho, Ji-Hoon, Wang, Xusheng, Xu, Beisi, Gupta, Pankaj, Fan, Yiping, Liu, Yu, Rusch, Michael, Griffiths, Lyra, Jeon, Jongrye, Freeman, Burgess B., III, Clay, Michael R., Pappo, Alberto, Easton, John, Shurtleff, Sheila, Shelat, Anang, Zhou, Xin, Boggs, Kristy, Mulder, Heather, Yergeau, Donald, Bahrami, Armita, Mardis, Elaine R., Wilson, Richard K., Zhang, Jinghui, Peng, Junmin, Downing, James R., and Dyer, Michael A.

Published
2018
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18. Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia

Author

Roberts, Kathryn G, Morin, Ryan D, Zhang, Jinghui, Hirst, Martin, Zhao, Yongjun, Su, Xiaoping, Chen, Shann-Ching, Payne-Turner, Debbie, Churchman, Michelle L, Harvey, Richard C, Chen, Xiang, Kasap, Corynn, Yan, Chunhua, Becksfort, Jared, Finney, Richard P, Teachey, David T, Maude, Shannon L, Tse, Kane, Moore, Richard, Jones, Steven, Mungall, Karen, Birol, Inanc, Edmonson, Michael N, Hu, Ying, Buetow, Kenneth E, Chen, I-Ming, Carroll, William L, Wei, Lei, Ma, Jing, Kleppe, Maria, Levine, Ross L, Garcia-Manero, Guillermo, Larsen, Eric, Shah, Neil P, Devidas, Meenakshi, Reaman, Gregory, Smith, Malcolm, Paugh, Steven W, Evans, William E, Grupp, Stephan A, Jeha, Sima, Pui, Ching-Hon, Gerhard, Daniela S, Downing, James R, Willman, Cheryl L, Loh, Mignon, Hunger, Stephen P, Marra, Marco A, and Mullighan, Charles G

Subjects
Pediatric Research Initiative, Childhood Leukemia, Orphan Drug, Hematology, Pediatric, Rare Diseases, Biotechnology, Genetics, Pediatric Cancer, Human Genome, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Base Sequence, Cell Transformation, Neoplastic, DNA Mutational Analysis, Enzyme Activation, Gene Expression Regulation, Leukemic, Gene Rearrangement, Genetic Predisposition to Disease, Humans, Mice, Molecular Sequence Data, Mutation, Oncogene Proteins, Fusion, Philadelphia Chromosome, Phosphorylation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, RNA, Messenger, Receptor, Platelet-Derived Growth Factor beta, Receptors, Cytokine, Recurrence, Risk Factors, Sequence Deletion, Signal Transduction, Trans-Activators, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2, and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2-negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.

Published
2012

19. A novel retinoblastoma therapy from genomic and epigenetic analyses.

Author

Zhang, Jinghui, Benavente, Claudia A, McEvoy, Justina, Flores-Otero, Jacqueline, Ding, Li, Chen, Xiang, Ulyanov, Anatoly, Wu, Gang, Wilson, Matthew, Wang, Jianmin, Brennan, Rachel, Rusch, Michael, Manning, Amity L, Ma, Jing, Easton, John, Shurtleff, Sheila, Mullighan, Charles, Pounds, Stanley, Mukatira, Suraj, Gupta, Pankaj, Neale, Geoff, Zhao, David, Lu, Charles, Fulton, Robert S, Fulton, Lucinda L, Hong, Xin, Dooling, David J, Ochoa, Kerri, Naeve, Clayton, Dyson, Nicholas J, Mardis, Elaine R, Bahrami, Armita, Ellison, David, Wilson, Richard K, Downing, James R, and Dyer, Michael A

Subjects
Cell Line, Animals, Humans, Mice, Retinoblastoma, Aneuploidy, Chromosomal Instability, Intracellular Signaling Peptides and Proteins, Retinoblastoma Protein, Protein Kinase Inhibitors, Xenograft Model Antitumor Assays, Sequence Analysis, DNA, Genomics, Cell Death, Cell Survival, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Mutation, Genes, Retinoblastoma, Protein-Tyrosine Kinases, Molecular Targeted Therapy, Syk Kinase, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Genes, Sequence Analysis, DNA, General Science & Technology
Abstract

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.

Published
2012

20. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase

Author

Kohlmann, Alexander, Kipps, Thomas J, Rassenti, Laura Z, Downing, James R, Shurtleff, Sheila A, Mills, Ken I, Gilkes, Amanda F, Hofmann, Wolf-Karsten, Basso, Giuseppe, Dell’Orto, Marta Campo, Foà, Robin, Chiaretti, Sabina, De Vos, John, Rauhut, Sonja, Papenhausen, Peter R, Hernández, Jesus M, Lumbreras, Eva, Yeoh, Allen E, Koay, Evelyn S, Li, Rachel, Liu, Wei-min, Williams, Paul M, Wieczorek, Lothar, and Haferlach, Torsten

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Research, Biotechnology, Rare Diseases, Cancer, Hematology, Adenocarcinoma, Breast Neoplasms, Carcinoma, Europe, Female, Gene Expression Profiling, Humans, Leukemia, Liver Neoplasms, Oligonucleotide Array Sequence Analysis, Pilot Projects, RNA, Reference Standards, Reproducibility of Results, Singapore, United States, microarray, gene expression profiling, leukaemia, standardization, diagnostics, Cardiorespiratory Medicine and Haematology, Immunology, Cardiovascular medicine and haematology
Abstract

Gene expression profiling has the potential to enhance current methods for the diagnosis of haematological malignancies. Here, we present data on 204 analyses from an international standardization programme that was conducted in 11 laboratories as a prephase to the Microarray Innovations in LEukemia (MILE) study. Each laboratory prepared two cell line samples, together with three replicate leukaemia patient lysates in two distinct stages: (i) a 5-d course of protocol training, and (ii) independent proficiency testing. Unsupervised, supervised, and r(2) correlation analyses demonstrated that microarray analysis can be performed with remarkably high intra-laboratory reproducibility and with comparable quality and reliability.

Published
2008

21. The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis

Author

Aldiri, Issam, Xu, Beisi, Wang, Lu, Chen, Xiang, Hiler, Daniel, Griffiths, Lyra, Valentine, Marc, Shirinifard, Abbas, Thiagarajan, Suresh, Sablauer, Andras, Barabas, Marie-Elizabeth, Zhang, Jiakun, Johnson, Dianna, Frase, Sharon, Zhou, Xin, Easton, John, Zhang, Jinghui, Mardis, Elaine R., Wilson, Richard K., Downing, James R., and Dyer, Michael A.

Published
2017
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22. Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations

Author

Brady, Samuel W., Liu, Yanling, Ma, Xiaotu, Gout, Alexander M., Hagiwara, Kohei, Zhou, Xin, Wang, Jian, Macias, Michael, Chen, Xiaolong, Easton, John, Mulder, Heather L., Rusch, Michael, Wang, Lu, Nakitandwe, Joy, Lei, Shaohua, Davis, Eric M., Naranjo, Arlene, Cheng, Cheng, Maris, John M., Downing, James R., Cheung, Nai-Kong V., Hogarty, Michael D., Dyer, Michael A., and Zhang, Jinghui

Published
2020
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24. PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia

Author

Gu, Zhaohui, Churchman, Michelle L., Roberts, Kathryn G., Moore, Ian, Zhou, Xin, Nakitandwe, Joy, Hagiwara, Kohei, Pelletier, Stephane, Gingras, Sebastien, Berns, Hartmut, Payne-Turner, Debbie, Hill, Ashley, Iacobucci, Ilaria, Shi, Lei, Pounds, Stanley, Cheng, Cheng, Pei, Deqing, Qu, Chunxu, Newman, Scott, Devidas, Meenakshi, Dai, Yunfeng, Reshmi, Shalini C., Gastier-Foster, Julie, Raetz, Elizabeth A., Borowitz, Michael J., Wood, Brent L., Carroll, William L., Zweidler-McKay, Patrick A., Rabin, Karen R., Mattano, Leonard A., Maloney, Kelly W., Rambaldi, Alessandro, Spinelli, Orietta, Radich, Jerald P., Minden, Mark D., Rowe, Jacob M., Luger, Selina, Litzow, Mark R., Tallman, Martin S., Racevskis, Janis, Zhang, Yanming, Bhatia, Ravi, Kohlschmidt, Jessica, Mrózek, Krzysztof, Bloomfield, Clara D., Stock, Wendy, Kornblau, Steven, Kantarjian, Hagop M., Konopleva, Marina, Evans, Williams E., Jeha, Sima, Pui, Ching-Hon, Yang, Jun, Paietta, Elisabeth, Downing, James R., Relling, Mary V., Zhang, Jinghui, Loh, Mignon L., Hunger, Stephen P., and Mullighan, Charles G.

Published
2019
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26. The genetic basis and cell of origin of mixed phenotype acute leukaemia

Author

Alexander, Thomas B., Gu, Zhaohui, Iacobucci, Ilaria, Dickerson, Kirsten, Choi, John K., Xu, Beisi, Payne-Turner, Debbie, Yoshihara, Hiroki, Loh, Mignon L., Horan, John, Buldini, Barbara, Basso, Giuseppe, Elitzur, Sarah, de Haas, Valerie, Zwaan, C. Michel, Yeoh, Allen, Reinhardt, Dirk, Tomizawa, Daisuke, Kiyokawa, Nobutaka, Lammens, Tim, De Moerloose, Barbara, Catchpoole, Daniel, Hori, Hiroki, Moorman, Anthony, Moore, Andrew S., Hrusak, Ondrej, Meshinchi, Soheil, Orgel, Etan, Devidas, Meenakshi, Borowitz, Michael, Wood, Brent, Heerema, Nyla A., Carrol, Andrew, Yang, Yung-Li, Smith, Malcolm A., Davidsen, Tanja M., Hermida, Leandro C., Gesuwan, Patee, Marra, Marco A., Ma, Yussanne, Mungall, Andrew J., Moore, Richard A., Jones, Steven J. M., Valentine, Marcus, Janke, Laura J., Rubnitz, Jeffrey E., Pui, Ching-Hon, Ding, Liang, Liu, Yu, Zhang, Jinghui, Nichols, Kim E., Downing, James R., Cao, Xueyuan, Shi, Lei, Pounds, Stanley, Newman, Scott, Pei, Deqing, Guidry Auvil, Jaime M., Gerhard, Daniela S., Hunger, Stephen P., Inaba, Hiroto, and Mullighan, Charles G.

Published
2018
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27. MYCN amplification and ATRX mutations are incompatible in neuroblastoma

Author

Zeineldin, Maged, Federico, Sara, Chen, Xiang, Fan, Yiping, Xu, Beisi, Stewart, Elizabeth, Zhou, Xin, Jeon, Jongrye, Griffiths, Lyra, Nguyen, Rosa, Norrie, Jackie, Easton, John, Mulder, Heather, Yergeau, Donald, Liu, Yanling, Wu, Jianrong, Van Ryn, Collin, Naranjo, Arlene, Hogarty, Michael D., Kamiński, Marcin M., Valentine, Marc, Pruett-Miller, Shondra M., Pappo, Alberto, Zhang, Jinghui, Clay, Michael R., Bahrami, Armita, Vogel, Peter, Lee, Seungjae, Shelat, Anang, Sarthy, Jay F., Meers, Michael P., George, Rani E., Mardis, Elaine R., Wilson, Richard K., Henikoff, Steven, Downing, James R., and Dyer, Michael A.

Published
2020
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28. Data from Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia

Author

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

Published
2023
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29. Supplementary Excel Tables from Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators

Author

Fornerod, Maarten, primary, Ma, Jing, primary, Noort, Sanne, primary, Liu, Yu, primary, Walsh, Michael P., primary, Shi, Lei, primary, Nance, Stephanie, primary, Liu, Yanling, primary, Wang, Yuanyuan, primary, Song, Guangchun, primary, Lamprecht, Tamara, primary, Easton, John, primary, Mulder, Heather L., primary, Yergeau, Donald, primary, Myers, Jacquelyn, primary, Kamens, Jennifer L., primary, Obeng, Esther A., primary, Pigazzi, Martina, primary, Jarosova, Marie, primary, Kelaidi, Charikleia, primary, Polychronopoulou, Sophia, primary, Lamba, Jatinder K., primary, Baker, Sharyn D., primary, Rubnitz, Jeffrey E., primary, Reinhardt, Dirk, primary, van den Heuvel-Eibrink, Marry M., primary, Locatelli, Franco, primary, Hasle, Henrik, primary, Klco, Jeffery M., primary, Downing, James R., primary, Zhang, Jinghui, primary, Pounds, Stanley, primary, Zwaan, C. Michel, primary, and Gruber, Tanja A., primary

Published
2023
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30. Supplementary Data from Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia

Author

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

Published
2023
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31. Supplementary Tables and Figures from Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators

Author

Fornerod, Maarten, primary, Ma, Jing, primary, Noort, Sanne, primary, Liu, Yu, primary, Walsh, Michael P., primary, Shi, Lei, primary, Nance, Stephanie, primary, Liu, Yanling, primary, Wang, Yuanyuan, primary, Song, Guangchun, primary, Lamprecht, Tamara, primary, Easton, John, primary, Mulder, Heather L., primary, Yergeau, Donald, primary, Myers, Jacquelyn, primary, Kamens, Jennifer L., primary, Obeng, Esther A., primary, Pigazzi, Martina, primary, Jarosova, Marie, primary, Kelaidi, Charikleia, primary, Polychronopoulou, Sophia, primary, Lamba, Jatinder K., primary, Baker, Sharyn D., primary, Rubnitz, Jeffrey E., primary, Reinhardt, Dirk, primary, van den Heuvel-Eibrink, Marry M., primary, Locatelli, Franco, primary, Hasle, Henrik, primary, Klco, Jeffery M., primary, Downing, James R., primary, Zhang, Jinghui, primary, Pounds, Stanley, primary, Zwaan, C. Michel, primary, and Gruber, Tanja A., primary

Published
2023
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32. Data from Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators

Author

Fornerod, Maarten, primary, Ma, Jing, primary, Noort, Sanne, primary, Liu, Yu, primary, Walsh, Michael P., primary, Shi, Lei, primary, Nance, Stephanie, primary, Liu, Yanling, primary, Wang, Yuanyuan, primary, Song, Guangchun, primary, Lamprecht, Tamara, primary, Easton, John, primary, Mulder, Heather L., primary, Yergeau, Donald, primary, Myers, Jacquelyn, primary, Kamens, Jennifer L., primary, Obeng, Esther A., primary, Pigazzi, Martina, primary, Jarosova, Marie, primary, Kelaidi, Charikleia, primary, Polychronopoulou, Sophia, primary, Lamba, Jatinder K., primary, Baker, Sharyn D., primary, Rubnitz, Jeffrey E., primary, Reinhardt, Dirk, primary, van den Heuvel-Eibrink, Marry M., primary, Locatelli, Franco, primary, Hasle, Henrik, primary, Klco, Jeffery M., primary, Downing, James R., primary, Zhang, Jinghui, primary, Pounds, Stanley, primary, Zwaan, C. Michel, primary, and Gruber, Tanja A., primary

Published
2023
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33. Table S6 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Author

Jeha, Sima, primary, Choi, John, primary, Roberts, Kathryn G., primary, Pei, Deqing, primary, Coustan-Smith, Elaine, primary, Inaba, Hiroto, primary, Rubnitz, Jeffrey E., primary, Ribeiro, Raul C., primary, Gruber, Tanja A., primary, Raimondi, Susana C., primary, Karol, Seth E., primary, Qu, Chunxu, primary, Brady, Samuel W., primary, Gu, Zhaohui, primary, Yang, Jun J., primary, Cheng, Cheng, primary, Downing, James R., primary, Evans, Williams E., primary, Relling, Mary V., primary, Campana, Dario, primary, Mullighan, Charles G., primary, and Pui, Ching-Hon, primary

Published
2023
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34. Tables S1-S5 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Author

Jeha, Sima, primary, Choi, John, primary, Roberts, Kathryn G., primary, Pei, Deqing, primary, Coustan-Smith, Elaine, primary, Inaba, Hiroto, primary, Rubnitz, Jeffrey E., primary, Ribeiro, Raul C., primary, Gruber, Tanja A., primary, Raimondi, Susana C., primary, Karol, Seth E., primary, Qu, Chunxu, primary, Brady, Samuel W., primary, Gu, Zhaohui, primary, Yang, Jun J., primary, Cheng, Cheng, primary, Downing, James R., primary, Evans, Williams E., primary, Relling, Mary V., primary, Campana, Dario, primary, Mullighan, Charles G., primary, and Pui, Ching-Hon, primary

Published
2023
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35. Data from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Author

Jeha, Sima, primary, Choi, John, primary, Roberts, Kathryn G., primary, Pei, Deqing, primary, Coustan-Smith, Elaine, primary, Inaba, Hiroto, primary, Rubnitz, Jeffrey E., primary, Ribeiro, Raul C., primary, Gruber, Tanja A., primary, Raimondi, Susana C., primary, Karol, Seth E., primary, Qu, Chunxu, primary, Brady, Samuel W., primary, Gu, Zhaohui, primary, Yang, Jun J., primary, Cheng, Cheng, primary, Downing, James R., primary, Evans, Williams E., primary, Relling, Mary V., primary, Campana, Dario, primary, Mullighan, Charles G., primary, and Pui, Ching-Hon, primary

Published
2023
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36. Supplementary Figure from Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia

Author

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

Published
2023
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37. Supplementary Data-1 from Clinical Significance of Novel Subtypes of Acute Lymphoblastic Leukemia in the Context of Minimal Residual Disease–Directed Therapy

Author

Jeha, Sima, primary, Choi, John, primary, Roberts, Kathryn G., primary, Pei, Deqing, primary, Coustan-Smith, Elaine, primary, Inaba, Hiroto, primary, Rubnitz, Jeffrey E., primary, Ribeiro, Raul C., primary, Gruber, Tanja A., primary, Raimondi, Susana C., primary, Karol, Seth E., primary, Qu, Chunxu, primary, Brady, Samuel W., primary, Gu, Zhaohui, primary, Yang, Jun J., primary, Cheng, Cheng, primary, Downing, James R., primary, Evans, Williams E., primary, Relling, Mary V., primary, Campana, Dario, primary, Mullighan, Charles G., primary, and Pui, Ching-Hon, primary

Published
2023
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38. Data from Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing

Author

Newman, Scott, primary, Nakitandwe, Joy, primary, Kesserwan, Chimene A., primary, Azzato, Elizabeth M., primary, Wheeler, David A., primary, Rusch, Michael, primary, Shurtleff, Sheila, primary, Hedges, Dale J., primary, Hamilton, Kayla V., primary, Foy, Scott G., primary, Edmonson, Michael N., primary, Thrasher, Andrew, primary, Bahrami, Armita, primary, Orr, Brent A., primary, Klco, Jeffery M., primary, Gu, Jiali, primary, Harrison, Lynn W., primary, Wang, Lu, primary, Clay, Michael R., primary, Ouma, Annastasia, primary, Silkov, Antonina, primary, Liu, Yanling, primary, Zhang, Zhaojie, primary, Liu, Yu, primary, Brady, Samuel W., primary, Zhou, Xin, primary, Chang, Ti-Cheng, primary, Pande, Manjusha, primary, Davis, Eric, primary, Becksfort, Jared, primary, Patel, Aman, primary, Wilkinson, Mark R., primary, Rahbarinia, Delaram, primary, Kubal, Manish, primary, Maciaszek, Jamie L., primary, Pastor, Victor, primary, Knight, Jay, primary, Gout, Alexander M., primary, Wang, Jian, primary, Gu, Zhaohui, primary, Mullighan, Charles G., primary, McGee, Rose B., primary, Quinn, Emily A., primary, Nuccio, Regina, primary, Mostafavi, Roya, primary, Gerhardt, Elsie L., primary, Taylor, Leslie M., primary, Valdez, Jessica M., primary, Hines-Dowell, Stacy J., primary, Pappo, Alberto S., primary, Robinson, Giles, primary, Johnson, Liza-Marie, primary, Pui, Ching-Hon, primary, Ellison, David W., primary, Downing, James R., primary, Zhang, Jinghui, primary, and Nichols, Kim E., primary

Published
2023
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39. Supplementary Tables S1-S5 from The Clonal Evolution of Metastatic Osteosarcoma as Shaped by Cisplatin Treatment

Author

Brady, Samuel W., primary, Ma, Xiaotu, primary, Bahrami, Armita, primary, Satas, Gryte, primary, Wu, Gang, primary, Newman, Scott, primary, Rusch, Michael, primary, Putnam, Daniel K., primary, Mulder, Heather L., primary, Yergeau, Donald A., primary, Edmonson, Michael N., primary, Easton, John, primary, Alexandrov, Ludmil B., primary, Chen, Xiang, primary, Mardis, Elaine R., primary, Wilson, Richard K., primary, Downing, James R., primary, Pappo, Alberto S., primary, Raphael, Benjamin J., primary, Dyer, Michael A., primary, and Zhang, Jinghui, primary

Published
2023
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40. Supplementary Figure S2 from Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing

Author

Newman, Scott, primary, Nakitandwe, Joy, primary, Kesserwan, Chimene A., primary, Azzato, Elizabeth M., primary, Wheeler, David A., primary, Rusch, Michael, primary, Shurtleff, Sheila, primary, Hedges, Dale J., primary, Hamilton, Kayla V., primary, Foy, Scott G., primary, Edmonson, Michael N., primary, Thrasher, Andrew, primary, Bahrami, Armita, primary, Orr, Brent A., primary, Klco, Jeffery M., primary, Gu, Jiali, primary, Harrison, Lynn W., primary, Wang, Lu, primary, Clay, Michael R., primary, Ouma, Annastasia, primary, Silkov, Antonina, primary, Liu, Yanling, primary, Zhang, Zhaojie, primary, Liu, Yu, primary, Brady, Samuel W., primary, Zhou, Xin, primary, Chang, Ti-Cheng, primary, Pande, Manjusha, primary, Davis, Eric, primary, Becksfort, Jared, primary, Patel, Aman, primary, Wilkinson, Mark R., primary, Rahbarinia, Delaram, primary, Kubal, Manish, primary, Maciaszek, Jamie L., primary, Pastor, Victor, primary, Knight, Jay, primary, Gout, Alexander M., primary, Wang, Jian, primary, Gu, Zhaohui, primary, Mullighan, Charles G., primary, McGee, Rose B., primary, Quinn, Emily A., primary, Nuccio, Regina, primary, Mostafavi, Roya, primary, Gerhardt, Elsie L., primary, Taylor, Leslie M., primary, Valdez, Jessica M., primary, Hines-Dowell, Stacy J., primary, Pappo, Alberto S., primary, Robinson, Giles, primary, Johnson, Liza-Marie, primary, Pui, Ching-Hon, primary, Ellison, David W., primary, Downing, James R., primary, Zhang, Jinghui, primary, and Nichols, Kim E., primary

Published
2023
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41. Data from St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem

Author

McLeod, Clay, primary, Gout, Alexander M., primary, Zhou, Xin, primary, Thrasher, Andrew, primary, Rahbarinia, Delaram, primary, Brady, Samuel W., primary, Macias, Michael, primary, Birch, Kirby, primary, Finkelstein, David, primary, Sunny, Jobin, primary, Mudunuri, Rahul, primary, Orr, Brent A., primary, Treadway, Madison, primary, Davidson, Bob, primary, Ard, Tracy K., primary, Chiao, Arthur, primary, Swistak, Andrew, primary, Wiggins, Stephanie, primary, Foy, Scott, primary, Wang, Jian, primary, Sioson, Edgar, primary, Wang, Shuoguo, primary, Michael, J. Robert, primary, Liu, Yu, primary, Ma, Xiaotu, primary, Patel, Aman, primary, Edmonson, Michael N., primary, Wilkinson, Mark R., primary, Frantz, Andrew M., primary, Chang, Ti-Cheng, primary, Tian, Liqing, primary, Lei, Shaohua, primary, Islam, S.M. Ashiqul, primary, Meyer, Christopher, primary, Thangaraj, Naina, primary, Tater, Pamella, primary, Kandali, Vijay, primary, Ma, Singer, primary, Nguyen, Tuan, primary, Serang, Omar, primary, McGuire, Irina, primary, Robison, Nedra, primary, Gentry, Darrell, primary, Tang, Xing, primary, Palmer, Lance E., primary, Wu, Gang, primary, Suh, Ed, primary, Tanner, Leigh, primary, McMurry, James, primary, Lear, Matthew, primary, Pappo, Alberto S., primary, Wang, Zhaoming, primary, Wilson, Carmen L., primary, Cheng, Yong, primary, Meshinchi, Soheil, primary, Alexandrov, Ludmil B., primary, Weiss, Mitchell J., primary, Armstrong, Gregory T., primary, Robison, Leslie L., primary, Yasui, Yutaka, primary, Nichols, Kim E., primary, Ellison, David W., primary, Bangur, Chaitanya, primary, Mullighan, Charles G., primary, Baker, Suzanne J., primary, Dyer, Michael A., primary, Miller, Geralyn, primary, Newman, Scott, primary, Rusch, Michael, primary, Daly, Richard, primary, Perry, Keith, primary, Downing, James R., primary, and Zhang, Jinghui, primary

Published
2023
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42. Supplementary Figures S1-S11 from The Clonal Evolution of Metastatic Osteosarcoma as Shaped by Cisplatin Treatment

Author

Brady, Samuel W., primary, Ma, Xiaotu, primary, Bahrami, Armita, primary, Satas, Gryte, primary, Wu, Gang, primary, Newman, Scott, primary, Rusch, Michael, primary, Putnam, Daniel K., primary, Mulder, Heather L., primary, Yergeau, Donald A., primary, Edmonson, Michael N., primary, Easton, John, primary, Alexandrov, Ludmil B., primary, Chen, Xiang, primary, Mardis, Elaine R., primary, Wilson, Richard K., primary, Downing, James R., primary, Pappo, Alberto S., primary, Raphael, Benjamin J., primary, Dyer, Michael A., primary, and Zhang, Jinghui, primary

Published
2023
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43. Data from The Clonal Evolution of Metastatic Osteosarcoma as Shaped by Cisplatin Treatment

Author

Brady, Samuel W., primary, Ma, Xiaotu, primary, Bahrami, Armita, primary, Satas, Gryte, primary, Wu, Gang, primary, Newman, Scott, primary, Rusch, Michael, primary, Putnam, Daniel K., primary, Mulder, Heather L., primary, Yergeau, Donald A., primary, Edmonson, Michael N., primary, Easton, John, primary, Alexandrov, Ludmil B., primary, Chen, Xiang, primary, Mardis, Elaine R., primary, Wilson, Richard K., primary, Downing, James R., primary, Pappo, Alberto S., primary, Raphael, Benjamin J., primary, Dyer, Michael A., primary, and Zhang, Jinghui, primary

Published
2023
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44. Supplementary Tables from Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing

Author

Newman, Scott, primary, Nakitandwe, Joy, primary, Kesserwan, Chimene A., primary, Azzato, Elizabeth M., primary, Wheeler, David A., primary, Rusch, Michael, primary, Shurtleff, Sheila, primary, Hedges, Dale J., primary, Hamilton, Kayla V., primary, Foy, Scott G., primary, Edmonson, Michael N., primary, Thrasher, Andrew, primary, Bahrami, Armita, primary, Orr, Brent A., primary, Klco, Jeffery M., primary, Gu, Jiali, primary, Harrison, Lynn W., primary, Wang, Lu, primary, Clay, Michael R., primary, Ouma, Annastasia, primary, Silkov, Antonina, primary, Liu, Yanling, primary, Zhang, Zhaojie, primary, Liu, Yu, primary, Brady, Samuel W., primary, Zhou, Xin, primary, Chang, Ti-Cheng, primary, Pande, Manjusha, primary, Davis, Eric, primary, Becksfort, Jared, primary, Patel, Aman, primary, Wilkinson, Mark R., primary, Rahbarinia, Delaram, primary, Kubal, Manish, primary, Maciaszek, Jamie L., primary, Pastor, Victor, primary, Knight, Jay, primary, Gout, Alexander M., primary, Wang, Jian, primary, Gu, Zhaohui, primary, Mullighan, Charles G., primary, McGee, Rose B., primary, Quinn, Emily A., primary, Nuccio, Regina, primary, Mostafavi, Roya, primary, Gerhardt, Elsie L., primary, Taylor, Leslie M., primary, Valdez, Jessica M., primary, Hines-Dowell, Stacy J., primary, Pappo, Alberto S., primary, Robinson, Giles, primary, Johnson, Liza-Marie, primary, Pui, Ching-Hon, primary, Ellison, David W., primary, Downing, James R., primary, Zhang, Jinghui, primary, and Nichols, Kim E., primary

Published
2023
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45. Supplementary Tables from St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem

Author

McLeod, Clay, primary, Gout, Alexander M., primary, Zhou, Xin, primary, Thrasher, Andrew, primary, Rahbarinia, Delaram, primary, Brady, Samuel W., primary, Macias, Michael, primary, Birch, Kirby, primary, Finkelstein, David, primary, Sunny, Jobin, primary, Mudunuri, Rahul, primary, Orr, Brent A., primary, Treadway, Madison, primary, Davidson, Bob, primary, Ard, Tracy K., primary, Chiao, Arthur, primary, Swistak, Andrew, primary, Wiggins, Stephanie, primary, Foy, Scott, primary, Wang, Jian, primary, Sioson, Edgar, primary, Wang, Shuoguo, primary, Michael, J. Robert, primary, Liu, Yu, primary, Ma, Xiaotu, primary, Patel, Aman, primary, Edmonson, Michael N., primary, Wilkinson, Mark R., primary, Frantz, Andrew M., primary, Chang, Ti-Cheng, primary, Tian, Liqing, primary, Lei, Shaohua, primary, Islam, S.M. Ashiqul, primary, Meyer, Christopher, primary, Thangaraj, Naina, primary, Tater, Pamella, primary, Kandali, Vijay, primary, Ma, Singer, primary, Nguyen, Tuan, primary, Serang, Omar, primary, McGuire, Irina, primary, Robison, Nedra, primary, Gentry, Darrell, primary, Tang, Xing, primary, Palmer, Lance E., primary, Wu, Gang, primary, Suh, Ed, primary, Tanner, Leigh, primary, McMurry, James, primary, Lear, Matthew, primary, Pappo, Alberto S., primary, Wang, Zhaoming, primary, Wilson, Carmen L., primary, Cheng, Yong, primary, Meshinchi, Soheil, primary, Alexandrov, Ludmil B., primary, Weiss, Mitchell J., primary, Armstrong, Gregory T., primary, Robison, Leslie L., primary, Yasui, Yutaka, primary, Nichols, Kim E., primary, Ellison, David W., primary, Bangur, Chaitanya, primary, Mullighan, Charles G., primary, Baker, Suzanne J., primary, Dyer, Michael A., primary, Miller, Geralyn, primary, Newman, Scott, primary, Rusch, Michael, primary, Daly, Richard, primary, Perry, Keith, primary, Downing, James R., primary, and Zhang, Jinghui, primary

Published
2023
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46. Supplementary Data from St. Jude Cloud: A Pediatric Cancer Genomic Data-Sharing Ecosystem

Author

McLeod, Clay, primary, Gout, Alexander M., primary, Zhou, Xin, primary, Thrasher, Andrew, primary, Rahbarinia, Delaram, primary, Brady, Samuel W., primary, Macias, Michael, primary, Birch, Kirby, primary, Finkelstein, David, primary, Sunny, Jobin, primary, Mudunuri, Rahul, primary, Orr, Brent A., primary, Treadway, Madison, primary, Davidson, Bob, primary, Ard, Tracy K., primary, Chiao, Arthur, primary, Swistak, Andrew, primary, Wiggins, Stephanie, primary, Foy, Scott, primary, Wang, Jian, primary, Sioson, Edgar, primary, Wang, Shuoguo, primary, Michael, J. Robert, primary, Liu, Yu, primary, Ma, Xiaotu, primary, Patel, Aman, primary, Edmonson, Michael N., primary, Wilkinson, Mark R., primary, Frantz, Andrew M., primary, Chang, Ti-Cheng, primary, Tian, Liqing, primary, Lei, Shaohua, primary, Islam, S.M. Ashiqul, primary, Meyer, Christopher, primary, Thangaraj, Naina, primary, Tater, Pamella, primary, Kandali, Vijay, primary, Ma, Singer, primary, Nguyen, Tuan, primary, Serang, Omar, primary, McGuire, Irina, primary, Robison, Nedra, primary, Gentry, Darrell, primary, Tang, Xing, primary, Palmer, Lance E., primary, Wu, Gang, primary, Suh, Ed, primary, Tanner, Leigh, primary, McMurry, James, primary, Lear, Matthew, primary, Pappo, Alberto S., primary, Wang, Zhaoming, primary, Wilson, Carmen L., primary, Cheng, Yong, primary, Meshinchi, Soheil, primary, Alexandrov, Ludmil B., primary, Weiss, Mitchell J., primary, Armstrong, Gregory T., primary, Robison, Leslie L., primary, Yasui, Yutaka, primary, Nichols, Kim E., primary, Ellison, David W., primary, Bangur, Chaitanya, primary, Mullighan, Charles G., primary, Baker, Suzanne J., primary, Dyer, Michael A., primary, Miller, Geralyn, primary, Newman, Scott, primary, Rusch, Michael, primary, Daly, Richard, primary, Perry, Keith, primary, Downing, James R., primary, and Zhang, Jinghui, primary

Published
2023
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50. 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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