A. Thomas Look, MD
Contact Information
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Appointments
Biography
A. Thomas Look, MD
Dr. Look received his MD in 1975 and residency training in pediatrics at the University of Michigan. He completed a fellowship in pediatric oncology at St. Jude Children's Research Hospital, where he trained in the molecular biology of cancer and eventually became chair of the Experimental Oncology Department. In 1999, he joined DFCI as vice chair for research in the Department of Pediatric Oncology.
Researcher
Physician
Recent Awards
- Second Annual Giulio J. D'Angio Lecturer, University of Pennsylvania Cancer Center 1999
- Award for Excellence in Pediatric Research, American Academy of Pediatrics 1995
- 2nd Annual Lecturer in Leukemia at The Hospital for Sick Children, Toronto, Canada 2000
- ASPHO Frank A. Oski Memorial Lectureship Award 2005
- Member, Association of American Physicians
2005
Research
Genetic Models of Leukemogenesis and Neuroblastoma
We are using zebrafish, in combination with murine and cell culture systems, to dissect developmental pathways subverted in human cancer. Zebrafish have been shown to share conserved pathways of development and disease pathogenesis with humans, thus permitting the identification of novel genes that are activated (oncogenes) or inactivated (tumor suppressors) during malignant transformation. We are using transgenic strategies to generate conditional zebrafish models of leukemias and solid tumors.We have identified novel genes regulating myelopoiesis, and are currently studying their respective contributions to the molecular pathogenesis of myelodysplastic syndrome and acute myeloid leukemia. We are applying similar approaches to study peripheral sympathetic nervous system development and to identify tumor suppressors in childhood neuroblastoma. We have also isolated a tumor-prone, mutant p53 zebrafish to study pathways involving this key regulator of DNA repair, cell cycle regulation, and apoptosis. p53 is the most commonly mutated gene in human cancers, and our zebrafish model is allowing us to study its role in several types of cancer.Our most advanced zebrafish model involves a transgenic line that develops T cell acute lymphoblastic leukemia (T-ALL). We are using this model to conduct one of the first cancer-related vertebrate genetic modifier screens, which will allow us to identify enhancers and suppressors of T-ALL progression. Using in vitro genome-scale location analysis (GSLA), we are also identifying the direct targets of oncogenic transcription factors and validating candidate target genes utilizing short interfering RNA strategies in human T-ALL cell lines. Through the combined use of these approaches, we hope to uncover novel genes and targets for the development of small-molecule inhibitors as therapeutics.In addition, we are studying apoptotic pathways controlled by the Slug transcription factor. We have shown that, in developing blood cells, DNA damage and p53 induction leads to the activation of Slug, which itself is a direct repressor of puma, a pro-apoptotic BH3-only protein. Mice deficient in both genes survive irradiation doses that are lethal to mice lacking Slug alone. Thus, Slug provides a novel mechanism downstream of p53 to ensure cell survival, rescuing damaged hematopoietic progenitors from programmed cell death, and allowing restorative repopulation of blood cells after radiation and other insults that cause DNA damage.
Publications
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Genetic predisposition to neuroblastoma results from a regulatory polymorphism that promotes the adrenergic cell state. J Clin Invest. 2023 05 15; 133(10). View in: Pubmed
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Genetic Predisposition to Neuroblastoma Results from a Regulatory Polymorphism that Promotes the Adrenergic Cell State. bioRxiv. 2023 Mar 01. View in: Pubmed
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Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates. Clin Cancer Res. 2023 03 01; 29(5):878-887. View in: Pubmed
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Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors. Br J Haematol. 2023 05; 201(3):489-501. View in: Pubmed
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p53 Pathway Inactivation Drives SMARCB1-deficient p53-wildtype Epithelioid Sarcoma Onset Indicating Therapeutic Vulnerability Through MDM2 Inhibition. Mol Cancer Ther. 2022 Nov 03; 21(11):1689-1700. View in: Pubmed
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EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified Neuroblastoma. Cancer Discov. 2022 03 01; 12(3):730-751. View in: Pubmed
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Association of allele-specific methylation of the ASNS gene with asparaginase sensitivity and prognosis in T-ALL. Blood Adv. 2022 01 11; 6(1):212-224. View in: Pubmed
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Retinoic acid rewires the adrenergic core regulatory circuitry of childhood neuroblastoma. Sci Adv. 2021 Oct 22; 7(43):eabe0834. View in: Pubmed
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Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma. Nat Commun. 2021 09 22; 12(1):5577. View in: Pubmed
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Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss. Oncogene. 2021 09; 40(38):5718-5729. View in: Pubmed
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Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma. Cancer Res. 2021 09 01; 81(17):4417-4430. View in: Pubmed
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Integrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL). Sci Rep. 2021 03 04; 11(1):5154. View in: Pubmed
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GAS7 Deficiency Promotes Metastasis in MYCN-Driven Neuroblastoma. Cancer Res. 2021 06 01; 81(11):2995-3007. View in: Pubmed
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Targeting ganglioneuromas with mTOR inhibitors. Mol Cell Oncol. 2021 Jan 10; 8(1):1856621. View in: Pubmed
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Correction: Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma. Leukemia. 2020 Nov; 34(11):3105. View in: Pubmed
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Ganglioneuromas are driven by activated AKT and can be therapeutically targeted with mTOR inhibitors. J Exp Med. 2020 10 05; 217(10). View in: Pubmed
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suz12 inactivation in p53- and nf1-deficient zebrafish accelerates the onset of malignant peripheral nerve sheath tumors and expands the spectrum of tumor types. Dis Model Mech. 2020 08 27; 13(8). View in: Pubmed
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ARID1A loss in neuroblastoma promotes the adrenergic-to-mesenchymal transition by regulating enhancer-mediated gene expression. Sci Adv. 2020 07; 6(29):eaaz3440. View in: Pubmed
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Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X. Nat Genet. 2020 08; 52(8):811-818. View in: Pubmed
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LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors. Proc Natl Acad Sci U S A. 2020 07 14; 117(28):16516-16526. View in: Pubmed
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Synthetic lethal targeting of TET2-mutant hematopoietic stem and progenitor cells (HSPCs) with TOP1-targeted drugs and PARP1 inhibitors. Leukemia. 2020 11; 34(11):2992-3006. View in: Pubmed
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Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2. Cell. 2020 04 30; 181(3):702-715.e20. View in: Pubmed
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Discovery of a selective inhibitor of doublecortin like kinase 1. Nat Chem Biol. 2020 06; 16(6):635-643. View in: Pubmed
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suz12 inactivation in p53 and nf1 deficient zebrafish accelerates the onset of MPNSTs and expands the spectrum of tumor types to include adenocarcinoma, leukemia, and soft tissue sarcoma. Dis Model Mech. 2020 Jan 01. View in: Pubmed
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ASCL1 is a MYCN- and LMO1-dependent member of the adrenergic neuroblastoma core regulatory circuitry. Nat Commun. 2019 12 09; 10(1):5622. View in: Pubmed
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Mechanisms underlying synergy between DNA topoisomerase I-targeted drugs and mTOR kinase inhibitors in NF1-associated malignant peripheral nerve sheath tumors. Oncogene. 2019 09; 38(39):6585-6598. View in: Pubmed
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High ENT1 and DCK gene expression levels are a potential biomarker to predict favorable response to nelarabine therapy in T-cell acute lymphoblastic leukemia. Hematol Oncol. 2019 Oct; 37(4):516-519. View in: Pubmed
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Disruption of asxl1 results in myeloproliferative neoplasms in zebrafish. Dis Model Mech. 2019 05 07; 12(5). View in: Pubmed
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Loss of atrx cooperates with p53-deficiency to promote the development of sarcomas and other malignancies. PLoS Genet. 2019 04; 15(4):e1008039. View in: Pubmed
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Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma. Leukemia. 2019 03; 33(3):696-709. View in: Pubmed
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Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry. Nat Genet. 2018 09; 50(9):1240-1246. View in: Pubmed
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The MCL1-specific inhibitor S63845 acts synergistically with venetoclax/ABT-199 to induce apoptosis in T-cell acute lymphoblastic leukemia cells. Leukemia. 2019 01; 33(1):262-266. View in: Pubmed
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JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia. J Exp Med. 2018 07 02; 215(7):1929-1945. View in: Pubmed
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Cross-Cohort Analysis Identifies a TEAD4-MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma. Cancer Discov. 2018 05; 8(5):582-599. View in: Pubmed
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Unraveling Neuroblastoma Pathogenesis with the Zebrafish. Cell Cycle. 2018; 17(4):395-396. View in: Pubmed
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MYC Drives a Subset of High-Risk Pediatric Neuroblastomas and Is Activated through Mechanisms Including Enhancer Hijacking and Focal Enhancer Amplification. Cancer Discov. 2018 03; 8(3):320-335. View in: Pubmed
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MYC-family protein overexpression and prominent nucleolar formation represent prognostic indicators and potential therapeutic targets for aggressive high-MKI neuroblastomas: a report from the children's oncology group. Oncotarget. 2018 Jan 19; 9(5):6416-6432. View in: Pubmed
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TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2017 11; 7(11):1336-1353. View in: Pubmed
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LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis. Cancer Cell. 2017 09 11; 32(3):310-323.e5. View in: Pubmed
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Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes. J Immunol. 2017 09 01; 199(5):1706-1715. View in: Pubmed
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Corrigendum: Small genomic insertions form enhancers that misregulate oncogenes. Nat Commun. 2017 06 01; 8:15797. View in: Pubmed
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Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation. Cell Rep. 2017 03 21; 18(12):2932-2942. View in: Pubmed
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Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia. Br J Haematol. 2017 04; 177(2):271-282. View in: Pubmed
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Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood. 2017 06 15; 129(24):3221-3226. View in: Pubmed
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The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma. Oncogene. 2017 07 06; 36(27):3852-3867. View in: Pubmed
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APOBEC signature mutation generates an oncogenic enhancer that drives LMO1 expression in T-ALL. Leukemia. 2017 10; 31(10):2057-2064. View in: Pubmed
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Small genomic insertions form enhancers that misregulate oncogenes. Nat Commun. 2017 02 09; 8:14385. View in: Pubmed
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Zebrafish models of leukemia. Methods Cell Biol. 2017; 138:563-592. View in: Pubmed
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Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia. Oncotarget. 2016 Dec 20; 7(51):84214-84227. View in: Pubmed
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Overexpression of PDGFRA cooperates with loss of NF1 and p53 to accelerate the molecular pathogenesis of malignant peripheral nerve sheath tumors. Oncogene. 2017 02 23; 36(8):1058-1068. View in: Pubmed
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View in: Pubmed
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KPT-8602, a second-generation inhibitor of XPO1-mediated nuclear export, is well tolerated and highly active against AML blasts and leukemia-initiating cells. Leukemia. 2017 01; 31(1):143-150. View in: Pubmed
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Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain. Elife. 2016 04 27; 5. View in: Pubmed
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View in: Pubmed
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Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Nat Commun. 2016 Jan 21; 7:10358. View in: Pubmed
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Malignant Peripheral Nerve Sheath Tumors. Adv Exp Med Biol. 2016; 916:495-530. View in: Pubmed
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Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature. 2015 Dec 17; 528(7582):418-21. View in: Pubmed
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From bench to patient: model systems in drug discovery. Dis Model Mech. 2015 Oct 01; 8(10):1171-4. View in: Pubmed
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HSP90 inhibition leads to degradation of the TYK2 kinase and apoptotic cell death in T-cell acute lymphoblastic leukemia. Leukemia. 2016 Jan; 30(1):219-28. View in: Pubmed
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Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2016 Jan; 30(1):190-9. View in: Pubmed
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A zebrafish model of myelodysplastic syndrome produced through tet2 genomic editing. Mol Cell Biol. 2015 Mar; 35(5):789-804. View in: Pubmed
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Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 2014 Dec 12; 346(6215):1373-7. View in: Pubmed
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Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol. 2014 Nov; 16(11):1080-91. View in: Pubmed
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Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia. Br J Haematol. 2015 Jan; 168(2):230-8. View in: Pubmed
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The chromatin remodeling factor CHD5 is a transcriptional repressor of WEE1. PLoS One. 2014; 9(9):e108066. View in: Pubmed
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Age-dependent prognostic effect by Mitosis-Karyorrhexis Index in neuroblastoma: a report from the Children's Oncology Group. Pediatr Dev Pathol. 2014 Nov-Dec; 17(6):441-9. View in: Pubmed
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L-Leucine improves the anaemia in models of Diamond Blackfan anaemia and the 5q- syndrome in a TP53-independent way. Br J Haematol. 2014 Nov; 167(4):524-528. View in: Pubmed
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Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells. Gastroenterology. 2014 Oct; 147(4):882-892.e8. View in: Pubmed
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Loss of function tp53 mutations do not accelerate the onset of myc-induced T-cell acute lymphoblastic leukaemia in the zebrafish. Br J Haematol. 2014 Jul; 166(1):84-90. View in: Pubmed
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Notch signaling: switching an oncogene to a tumor suppressor. Blood. 2014 Apr 17; 123(16):2451-9. View in: Pubmed
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Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia. Leukemia. 2014 Sep; 28(9):1819-27. View in: Pubmed
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Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. J Clin Invest. 2014 Feb; 124(2):644-55. View in: Pubmed
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c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood. 2014 Feb 13; 123(7):1040-50. View in: Pubmed
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Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors. Haematologica. 2014 Jan; 99(1):94-102. View in: Pubmed
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Neuroblastoma of undifferentiated subtype, prognostic significance of prominent nucleolar formation, and MYC/MYCN protein expression: a report from the Children's Oncology Group. Cancer. 2013 Oct 15; 119(20):3718-26. View in: Pubmed
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MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy. Elife. 2013 Jul 16; 2:e00825. View in: Pubmed
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The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29; 210(8):1545-57. View in: Pubmed
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Discovery of a selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol. 2013 Jul 19; 8(7):1423-8. View in: Pubmed
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TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013 May; 3(5):564-77. View in: Pubmed
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The requirement for cyclin D function in tumor maintenance. Cancer Cell. 2012 Oct 16; 22(4):438-51. View in: Pubmed
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Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood. 2012 Nov 01; 120(18):3764-73. View in: Pubmed
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Distinct and dynamic requirements for mTOR signaling in hematopoiesis and leukemogenesis. Cell Stem Cell. 2012 Sep 07; 11(3):281-2. View in: Pubmed
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Ccdc94 protects cells from ionizing radiation by inhibiting the expression of p53. PLoS Genet. 2012; 8(8):e1002922. View in: Pubmed
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Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. Cancer Cell. 2012 Aug 14; 22(2):209-21. View in: Pubmed
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Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia. 2013 Jan; 27(1):66-74. View in: Pubmed
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PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling. Mol Cell. 2012 Sep 14; 47(5):681-93. View in: Pubmed
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Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development. Dis Model Mech. 2012 Nov; 5(6):881-94. View in: Pubmed
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Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia. Nat Med. 2012 Jul; 18(7):1118-22. View in: Pubmed
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NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches. PLoS One. 2012; 7(6):e39725. View in: Pubmed
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Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer. 2013 Mar; 60(3):363-70. View in: Pubmed
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L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood. 2012 Sep 13; 120(11):2214-24. View in: Pubmed
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Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency. Leukemia. 2012 Sep; 26(9):2069-78. View in: Pubmed
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Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012 Mar 20; 21(3):362-73. View in: Pubmed
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Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics. J Biol Chem. 2012 Mar 23; 287(13):9742-9752. View in: Pubmed
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Discovery of a secreted tumor suppressor provides a promising therapeutic strategy for follicular lymphoma. Cancer Cell. 2011 Nov 15; 20(5):559-61. View in: Pubmed
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Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development. 2011 Oct; 138(20):4555-64. View in: Pubmed
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Aberrant AKT activation drives well-differentiated liposarcoma. Proc Natl Acad Sci U S A. 2011 Sep 27; 108(39):16386-91. View in: Pubmed
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p63 mediates an apoptotic response to pharmacological and disease-related ER stress in the developing epidermis. Dev Cell. 2011 Sep 13; 21(3):492-505. View in: Pubmed
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The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia. Blood. 2011 Oct 13; 118(15):4169-73. View in: Pubmed
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NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis. Br J Haematol. 2011 Oct; 155(2):167-81. View in: Pubmed
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Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. J Exp Med. 2011 Aug 01; 208(8):1595-603. View in: Pubmed
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Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AML. Blood. 2011 Jul 28; 118(4):903-15. View in: Pubmed
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Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL. J Exp Med. 2011 Apr 11; 208(4):663-75. View in: Pubmed
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cpsf1 is required for definitive HSC survival in zebrafish. Blood. 2011 Apr 14; 117(15):3996-4007. View in: Pubmed
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Zebrafish as a model for the study of human cancer. Methods Cell Biol. 2011; 105:309-37. View in: Pubmed
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mll ortholog containing functional domains of human MLL is expressed throughout the zebrafish lifespan and in haematopoietic tissues. Br J Haematol. 2011 Feb; 152(3):307-21. View in: Pubmed
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Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb. Leukemia. 2011 Mar; 25(3):506-14. View in: Pubmed
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T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010 Oct 19; 18(4):353-66. View in: Pubmed
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Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. 2010 Sep 30; 363(14):1313-23. View in: Pubmed
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Oligodendrocyte progenitor cell numbers and migration are regulated by the zebrafish orthologs of the NF1 tumor suppressor gene. Hum Mol Genet. 2010 Dec 01; 19(23):4643-53. View in: Pubmed
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Absence of biallelic TCRgamma deletion predicts early treatment failure in pediatric T-cell acute lymphoblastic leukemia. J Clin Oncol. 2010 Aug 20; 28(24):3816-23. View in: Pubmed
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ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. J Exp Med. 2010 Jul 05; 207(7):1369-80. View in: Pubmed
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Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). Blood. 2010 Aug 12; 116(6):962-70. View in: Pubmed
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Phosphatase-dependent and -independent functions of Shp2 in neural crest cells underlie LEOPARD syndrome pathogenesis. Dev Cell. 2010 May 18; 18(5):750-62. View in: Pubmed
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Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010 Jun 10; 115(23):4707-14. View in: Pubmed
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SNP array analysis in hematologic malignancies: avoiding false discoveries. Blood. 2010 May 27; 115(21):4157-61. View in: Pubmed
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Expression of the cytoplasmic NPM1 mutant (NPMc+) causes the expansion of hematopoietic cells in zebrafish. Blood. 2010 Apr 22; 115(16):3329-40. View in: Pubmed
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Inactivation of LEF1 in T-cell acute lymphoblastic leukemia. Blood. 2010 Apr 08; 115(14):2845-51. View in: Pubmed
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Studying peripheral sympathetic nervous system development and neuroblastoma in zebrafish. Methods Cell Biol. 2010; 100:127-52. View in: Pubmed
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Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia. Blood. 2010 Mar 04; 115(9):1735-45. View in: Pubmed
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Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo. J Exp Med. 2009 Dec 21; 206(13):2977-86. View in: Pubmed
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Cardiac and vascular functions of the zebrafish orthologues of the type I neurofibromatosis gene NFI. Proc Natl Acad Sci U S A. 2009 Dec 29; 106(52):22305-10. View in: Pubmed
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Up-regulation of survivin by the E2A-HLF chimera is indispensable for the survival of t(17;19)-positive leukemia cells. J Biol Chem. 2010 Jan 15; 285(3):1850-60. View in: Pubmed
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Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG. Pediatr Blood Cancer. 2009 Oct; 53(4):563-9. View in: Pubmed
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Emi1 maintains genomic integrity during zebrafish embryogenesis and cooperates with p53 in tumor suppression. Mol Cell Biol. 2009 Nov; 29(21):5911-22. View in: Pubmed
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The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish. Development. 2009 Aug; 136(15):2591-600. View in: Pubmed
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A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 2009 Jun 18; 459(7249):996-9. View in: Pubmed
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High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. Blood. 2009 Jul 16; 114(3):647-50. View in: Pubmed
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Comparison of primary neuroblastoma tumors and derivative early-passage cell lines using genome-wide single nucleotide polymorphism array analysis. Cancer Res. 2009 May 15; 69(10):4143-9. View in: Pubmed
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Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia. 2009 Sep; 23(9):1605-13. View in: Pubmed
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CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Mol Cancer. 2009 Apr 16; 8:24. View in: Pubmed
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Inhibition of NOTCH signaling by gamma secretase inhibitor engages the RB pathway and elicits cell cycle exit in T-cell acute lymphoblastic leukemia cells. Cancer Res. 2009 Apr 01; 69(7):3060-8. View in: Pubmed
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Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev Anticancer Ther. 2009 Mar; 9(3):331-56. View in: Pubmed
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Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009 Mar 27; 104(6):733-41. View in: Pubmed
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Construction and application of a zebrafish array comparative genomic hybridization platform. Genes Chromosomes Cancer. 2009 Feb; 48(2):155-70. View in: Pubmed
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Muscle degeneration and leukocyte infiltration caused by mutation of zebrafish Fad24. Dev Dyn. 2009 Jan; 238(1):86-99. View in: Pubmed
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Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008 Oct 16; 455(7215):975-8. View in: Pubmed
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In vivo interstitial migration of primitive macrophages mediated by JNK-matrix metalloproteinase 13 signaling in response to acute injury. J Immunol. 2008 Aug 01; 181(3):2155-64. View in: Pubmed
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Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3. Cell. 2008 May 30; 133(5):864-77. View in: Pubmed
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BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell Death Differ. 2008 Jun; 15(6):1063-72. View in: Pubmed
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Acute lymphoblastic leukaemia. Lancet. 2008 Mar 22; 371(9617):1030-43. View in: Pubmed
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Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish. Oncogene. 2008 Jul 10; 27(30):4242-8. View in: Pubmed
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The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev. 2008 Apr 01; 22(7):884-93. View in: Pubmed
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SOS1 mutations are rare in human malignancies: implications for Noonan Syndrome patients. Genes Chromosomes Cancer. 2008 Mar; 47(3):253-9. View in: Pubmed
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Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood. 2008 May 01; 111(9):4716-22. View in: Pubmed
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Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: a report from the Children's Oncology Group. J Clin Oncol. 2008 Feb 20; 26(6):913-8. View in: Pubmed
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Alu elements mediate MYB gene tandem duplication in human T-ALL. J Exp Med. 2007 Dec 24; 204(13):3059-66. View in: Pubmed
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Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell. Cancer Res. 2007 Dec 01; 67(23):11234-43. View in: Pubmed
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NOTCH and PI3K-AKT pathways intertwined. Cancer Cell. 2007 Nov; 12(5):411-3. View in: Pubmed
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Mechanisms of transcription factor deregulation in lymphoid cell transformation. Oncogene. 2007 Oct 15; 26(47):6838-49. View in: Pubmed
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Live imaging of chronic inflammation caused by mutation of zebrafish Hai1. J Cell Sci. 2007 Oct 01; 120(Pt 19):3372-83. View in: Pubmed
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A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors. Genes Dev. 2007 Sep 01; 21(17):2131-6. View in: Pubmed
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FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med. 2007 Aug 06; 204(8):1813-24. View in: Pubmed
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Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. Br J Haematol. 2007 Jul; 138(2):169-75. View in: Pubmed
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Targeting transcription factors in acute leukemia in children. Curr Drug Targets. 2007 Jun; 8(6):727-37. View in: Pubmed
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Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays. PLoS One. 2007 Feb 28; 2(2):e255. View in: Pubmed
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Beta-catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation. Blood. 2007 Jun 15; 109(12):5463-72. View in: Pubmed
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Dominant-interfering C/EBPalpha stimulates primitive erythropoiesis in zebrafish. Exp Hematol. 2007 Feb; 35(2):230-9. View in: Pubmed
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Zebrafish as a powerful vertebrate model system for in vivo studies of cell death. Semin Cancer Biol. 2007 Apr; 17(2):154-65. View in: Pubmed
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Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med. 2007 Jan; 13(1):78-83. View in: Pubmed
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NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci U S A. 2006 Nov 28; 103(48):18261-6. View in: Pubmed
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Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2006 May; 6(5):347-59. View in: Pubmed
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Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Dev Biol. 2006 Apr 01; 292(1):174-88. View in: Pubmed
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Small molecules thwart crash and burn. Nat Chem Biol. 2005 Dec; 1(7):351-3. View in: Pubmed
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Activating Notch1 mutations in mouse models of T-ALL. Blood. 2006 Jan 15; 107(2):781-5. View in: Pubmed
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Zebrafish as a model for myelopoiesis during embryogenesis. Exp Hematol. 2005 Sep; 33(9):997-1006. View in: Pubmed
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Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. 2005 Sep 20; 23(27):6466-73. View in: Pubmed
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The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. 2005 Nov 15; 106(10):3377-9. View in: Pubmed
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CD34+ cell selection is required to assess HOXA9 expression levels in patients with myelodysplastic syndrome. Br J Haematol. 2005 Jul; 130(1):83-6. View in: Pubmed
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Evidence for an age cut-off greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group (COG). J Clin Oncol. 2005 Jun; 23(16_suppl):8500. View in: Pubmed
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A phase I study of decitabine (DCT) in combination with doxorubicin (DOX) and cyclophosphamide (CTX) in the treatment of relapsed or refractory solid tumors: A Children's Oncology Group Study. J Clin Oncol. 2005 Jun; 23(16_suppl):8530. View in: Pubmed
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Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2005 Apr 26; 102(17):6068-73. View in: Pubmed
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The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival. J Exp Med. 2005 Feb 21; 201(4):603-14. View in: Pubmed
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BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol. 2005 Feb 08; 15(3):249-54. View in: Pubmed
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tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. Proc Natl Acad Sci U S A. 2005 Jan 11; 102(2):407-12. View in: Pubmed
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Molecular Pathogenesis of MDS. Hematology Am Soc Hematol Educ Program. 2005; 156-60. View in: Pubmed
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Interplay of pu.1 and gata1 determines myelo-erythroid progenitor cell fate in zebrafish. Dev Cell. 2005 Jan; 8(1):97-108. View in: Pubmed
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Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish. Blood. 2005 Apr 15; 105(8):3278-85. View in: Pubmed
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Molecular pathways in T-cell acute lympho-blastic leukemia: ramifications for therapy. Clin Adv Hematol Oncol. 2004 Dec; 2(12):779-80. View in: Pubmed
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DNA microarrays in the diagnosis and management of acute lymphoblastic leukemia. Int J Hematol. 2004 Dec; 80(5):395-400. View in: Pubmed
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Hematopoietic gene expression profile in zebrafish kidney marrow. Proc Natl Acad Sci U S A. 2004 Nov 16; 101(46):16240-5. View in: Pubmed
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Targeted expression of human MYCN selectively causes pancreatic neuroendocrine tumors in transgenic zebrafish. Cancer Res. 2004 Oct 15; 64(20):7256-62. View in: Pubmed
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Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004 Oct 08; 306(5694):269-71. View in: Pubmed
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Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 2004 Oct; 36(10):1084-9. View in: Pubmed
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Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation. Blood. 2004 Sep 01; 104(5):1298-305. View in: Pubmed
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In vivo tracking of T cell development, ablation, and engraftment in transgenic zebrafish. Proc Natl Acad Sci U S A. 2004 May 11; 101(19):7369-74. View in: Pubmed
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The use of zebrafish to understand immunity. Immunity. 2004 Apr; 20(4):367-79. View in: Pubmed
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Activating FLT3 mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias. Blood. 2004 Jul 15; 104(2):558-60. View in: Pubmed
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The pu.1 promoter drives myeloid gene expression in zebrafish. Blood. 2004 Sep 01; 104(5):1291-7. View in: Pubmed
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Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet. 2004 Feb 14; 363(9408):535-6. View in: Pubmed
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Lessons from transgenic zebrafish expressing the green fluorescent protein (GFP) in the myeloid lineage. Methods Cell Biol. 2004; 77:333-47. View in: Pubmed
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Zebrafish sperm cryopreservation. Methods Cell Biol. 2004; 77:645-59. View in: Pubmed
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Development of the peripheral sympathetic nervous system in zebrafish. Methods Cell Biol. 2004; 76:237-60. View in: Pubmed
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Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein. Blood. 2004 Apr 15; 103(8):3185-91. View in: Pubmed
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Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis. Dev Cell. 2003 Dec; 5(6):903-14. View in: Pubmed
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IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL. Blood. 2004 Mar 01; 103(5):1891-900. View in: Pubmed
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Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia. Blood. 2004 Mar 01; 103(5):1909-11. View in: Pubmed
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Zebrafish as a model organism for blood diseases. Br J Haematol. 2003 Nov; 123(4):568-76. View in: Pubmed
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Zebrafish sperm cryopreservation with N,N-dimethylacetamide. Biotechniques. 2003 Nov; 35(5):956-8, 960, 962 passim. View in: Pubmed
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Gene expression profiling in T-cell acute lymphoblastic leukemia. Semin Hematol. 2003 Oct; 40(4):274-80. View in: Pubmed
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Turning on a dimer: new insights into MLL chimeras. Cancer Cell. 2003 Aug; 4(2):81-3. View in: Pubmed
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Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood. 2003 Jul 01; 102(1):262-8. View in: Pubmed
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Myc-induced T cell leukemia in transgenic zebrafish. Science. 2003 Feb 07; 299(5608):887-90. View in: Pubmed
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No evidence for the presence of an imprinted neuroblastoma suppressor gene within chromosome sub-band 1p36.3. Cancer Res. 2002 Nov 15; 62(22):6481-4. View in: Pubmed
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Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell. 2002 Oct; 2(4):279-88. View in: Pubmed
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Molecular cloning and developmental expression of Tlx (Hox11) genes in zebrafish (Danio rerio). Mech Dev. 2002 Sep; 117(1-2):243-8. View in: Pubmed
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A leukemogenic twist for GATA1. Nat Genet. 2002 Sep; 32(1):83-4. View in: Pubmed
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Evolutionary conservation of zebrafish linkage group 14 with frequently deleted regions of human chromosome 5 in myeloid malignancies. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):6136-41. View in: Pubmed
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Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002 Feb; 1(1):75-87. View in: Pubmed
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E2A-HLF usurps control of evolutionarily conserved survival pathways. Oncogene. 2001 Sep 10; 20(40):5718-25. View in: Pubmed
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The E2A-HLF oncoprotein activates Groucho-related genes and suppresses Runx1. Mol Cell Biol. 2001 Sep; 21(17):5935-45. View in: Pubmed
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Myelopoiesis in the zebrafish, Danio rerio. Blood. 2001 Aug 01; 98(3):643-51. View in: Pubmed
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Zebrafish myelopoiesis and blood cell development. Curr Opin Hematol. 2001 Jul; 8(4):245-51. View in: Pubmed
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The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia. 2001 Jul; 15(7):1081-8. View in: Pubmed
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Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors. Mol Cell Biol. 2001 Feb; 21(3):854-64. View in: Pubmed
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Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia. Semin Hematol. 2000 Oct; 37(4):381-95. View in: Pubmed
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Parental smoking and alcohol consumption and risk of neuroblastoma. Cancer Epidemiol Biomarkers Prev. 2000 Sep; 9(9):967-72. View in: Pubmed
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Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas. Cell Growth Differ. 1999 Jan; 10(1):35-42. View in: Pubmed
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Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 1998 Nov 10; 95(23):13765-70. View in: Pubmed
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Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family. Dev Biol. 1997 Mar 15; 183(2):166-82. View in: Pubmed
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Identification and characterization of neogenin, a DCC-related gene. Oncogene. 1997 Mar 13; 14(10):1129-36. View in: Pubmed
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cDNA cloning, tissue distribution, and chromosomal localization of myelodysplasia/myeloid leukemia factor 2 (MLF2). Genomics. 1996 Jul 15; 35(2):392-6. View in: Pubmed
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Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). Mol Cell Biol. 1994 Dec; 14(12):8085-95. View in: Pubmed
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Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key! Blood. 1993 Aug 15; 82(4):1052-70. View in: Pubmed
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