Now showing items 1-14 of 14

    • Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax 

      Montero, Joan; Stephansky, Jason; Cai, Tianyu; Griffin, Gabriel Kenneth; Cabal-Hierro, Lucia; Togami, Katsuhiro; Hogdal, Leah J.; Galinsky, Ilene; Morgan, Elizabeth Amy; Aster, Jon Christopher; Davids, Matthew Steven; Leboeuf, Nicole Renee; Stone, Richard Maury; Konopleva, Marina; Pemmaraju, Naveen; Letai, Anthony George; Lane, Andrew Alan (American Association for Cancer Research (AACR), 2016)
      Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy with dismal outcomes for which no standard therapy exists. We found that primary BPDCN cells were dependent on the anti-apoptotic ...
    • Characterization of activating mutations of NOTCH3 in T cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies 

      Bernasconi-Elias, Paula; Hu, Tiancen; Jenkins, David; Firestone, Brant; Gans, Sara; Kurth, Esther; Capodieci, Paola; Deplazes-Lauber, Joelle; Petropoulos, Konstantin; Thiel, Phillip; Ponsel, Dirk; Choi, Sung Hee; LeMotte, Peter; London, Anne; Goetcshkes, Margaret; Nolin, Erin; Jones, Michael D.; Slocum, Kelly; Kluk, Michael J.; Weinstock, David M.; Christodoulou, Alexandra; Weinberg, Olga; Jaehrling, Jan; Ettenberg, Seth A.; Buckler, Alan; Blacklow, Stephen C.; Aster, Jon C.; Fryer, Christy J. (2016)
      Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, ...
    • Comprehensive analyses of tumor immunity: implications for cancer immunotherapy 

      Li, Bo; Severson, Eric; Pignon, Jean-Christophe; Zhao, Haoquan; Li, Taiwen; Novak, Jesse; Jiang, Peng; Shen, Hui; Aster, Jon C.; Rodig, Scott; Signoretti, Sabina; Liu, Jun S.; Liu, X. Shirley (BioMed Central, 2016)
      Background: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are ...
    • Epigenetics of TET2 Loss in Myelodysplastic Syndromes 

      Lord, Allegra (2015-05-18)
      Myelodysplastic syndromes (MDS) are a class of myeloid malignancy characterized by peripheral blood cytopenias and impaired hematopoietic differentiation. Our understanding of the molecular basis of MDS has improved ...
    • Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry 

      Kluk, Michael J.; Ashworth, Todd; Wang, Hongfang; Knoechel, Birgit; Mason, Emily F.; Morgan, Elizabeth A.; Dorfman, David; Pinkus, Geraldine; Weigert, Oliver; Hornick, Jason L.; Chirieac, Lucian R.; Hirsch, Michelle; Oh, David J.; South, Andrew P.; Leigh, Irene M.; Pourreyron, Celine; Cassidy, Andrew J.; DeAngelo, Daniel J.; Weinstock, David M.; Krop, Ian E.; Dillon, Deborah; Brock, Jane E.; Lazar, Alexander J. F.; Peto, Myron; Cho, Raymond J.; Stoeck, Alexander; Haines, Brian B.; Sathayanrayanan, Sriram; Rodig, Scott; Aster, Jon C. (Public Library of Science, 2013)
      Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been ...
    • Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing 

      Heckl, Dirk; Kowalczyk, Monika S.; Yudovich, David; Belizaire, Roger; Puram, Rishi V.; McConkey, Marie E.; Thielke, Anne; Aster, Jon C.; Regev, Aviv; Ebert, Benjamin L. (2014)
      Genome sequencing studies have shown that human malignancies often bear mutations in four or more driver genes1, but it is difficult to recapitulate this degree of genetic complexity in mouse models using conventional ...
    • High-Level IGF1R Expression is Required for Leukemia-Initiating Cell Activity in T-ALL and is Supported by Notch Signaling 

      Medyouf, Hind; Gusscott, Samuel; Wai, Carol; Nemirovsky, Oksana; Trumpp, Andreas; Pflumio, Francoise; Carboni, Joan; Gottardis, Marco; Pollak, Michael; Holzenberger, Martin; Weng, Andrew P.; Wang, Hongfang; Tseng, Jen-Chieh; Kung, Andrew Li-Jen; Aster, Jon Christopher (Rockefeller University Press, 2011)
      T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer of immature T cells that often shows aberrant activation of Notch1 and PI3K–Akt pathways. Although mutations that activate PI3K–Akt signaling have previously ...
    • A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B and T cell malignancies 

      Ortega, Manoela; Bhatnagar, Harshita; Lin, An-Ping; Wang, Long; Aster, Jon C; Sill, Heinz; Aguiar, Ricardo C T (2014)
      Growing evidence suggests that microRNAs facilitate the cross-talk between transcriptional modules and signal transduction pathways. MYC and NOTCH1 contribute to the pathogenesis of lymphoid malignancies. NOTCH induces ...
    • Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11 

      Ngondo-Mbongo, Richard Patryk; Myslinski, Evelyne; Aster, Jon Christopher; Carbon, Philippe (Oxford University Press, 2013)
      ZNF143 is a zinc-finger protein involved in the transcriptional regulation of both coding and non-coding genes from polymerase II and III promoters. Our study deciphers the genome-wide regulatory role of ZNF143 in relation ...
    • Network analysis of gene essentiality in functional genomics experiments 

      Jiang, Peng; Wang, Hongfang; Li, Wei; Zang, Chongzhi; Li, Bo; Wong, Yinling J.; Meyer, Cliff; Liu, Jun S.; Aster, Jon C.; Liu, X. Shirley (BioMed Central, 2015)
      Many genomic techniques have been developed to study gene essentiality genome-wide, such as CRISPR and shRNA screens. Our analyses of public CRISPR screens suggest protein interaction networks, when integrated with gene ...
    • NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis 

      South, Andrew P; Purdie, Karin J; Watt, Stephen A; Haldenby, Sam; den Breems, Nicoline; Dimon, Michelle; Arron, Sarah T; Kluk, Michael J; Aster, Jon C; McHugh, Angela; Xue, Dylan J; Dayal, Jasbani HS; Robinson, Kim S; Rizvi, SM Hasan; Proby, Charlotte M; Harwood, Catherine A; Leigh, Irene M (2014)
      Cutaneous SCC (cSCC) is the most frequent skin cancer with metastatic potential and can manifest rapidly as a common side effect in patients receiving systemic kinase inhibitors. Here we use massively parallel exome and ...
    • A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors 

      Sharma, Ankur; Gadkari, Rupali A; Ramakanth, Satthenapalli V; Padmanabhan, Krishnanand; Madhumathi, Davanam S; Devi, Lakshmi; Appaji, Lingappa; Aster, Jon C; Rangarajan, Annapoorni; Dighe, Rajan R (Nature Publishing Group, 2015)
      Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The ...
    • An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma 

      Drier, Yotam; Cotton, Matthew J.; Williamson, Kaylyn E.; Gillespie, Shawn M.; Ryan, Russell J.H.; Kluk, Michael J.; Carey, Christopher D.; Rodig, Scott J.; Sholl, Lynette M; Afrogheh, Amir H.; Faquin, William C.; Queimado, Lurdes; Qi, Jun; Wick, Michael J.; El-Naggar, Adel K.; Bradner, James E.; Moskaluk, Christopher A.; Aster, Jon C.; Knoechel, Birgit; Bernstein, Bradley E. (2016)
      Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the ...
    • PKCθ Regulates T-Cell Leukemia-Initiating Activity via Reactive Oxygen Species 

      Giambra, Vincenzo; Jenkins, Christopher R.; Wang, Hongfang; Lam, Sonya H.; Shevchuk, Olena O.; Nemirovsky, Oksana; Wai, Carol; Gusscott, Sam; Chiang, Mark Y.; Aster, Jon C.; Humphries, R. Keith; Eaves, Connie; Weng, Andrew P. (2013)
      Reactive oxygen species (ROS), a by-product of cellular metabolism, damage intracellular macromolecules and, in excess, can promote normal hematopoietic stem cell differentiation and exhaustion1–3. However, mechanisms that ...