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217 results on '"Loeb, Keith R."'

1. Corrigendum

Author

Le, Quy, Hadland, Brandon, Smith, Jenny L., Leonti, Amanda, Huang, Benjamin J., Ries, Rhonda, Hylkema, Tiffany A., Castro, Sommer, Tang, Thao T., McKay, Cyd N., Perkins, LaKeisha, Pardo, Laura, Sarthy, Jay, Beckman, Amy K., Williams, Robin, Idemmili, Rhonda, Furlan, Scott, Ishida, Takashi, Call, Lindsey, Srivastava, Shivani, Loeb, Anisha M., Milano, Filippo, Imren, Suzan, Morris, Shelli M., Pakiam, Fiona, Olson, Jim M., Loken, Michael R., Brodersen, Lisa, Riddell, Stanley R., Tarlock, Katherine, Bernstein, Irwin D., Loeb, Keith R., and Meshinchi, Soheil

Subjects
Health care industry
Abstract

Original citation: J Clin Invest. 2022;132(22):e157101. https://doi.org/10.1172/JCn57101. During the preparation of Supplemental Figure 12A, an image for day 35 was inadvertently used instead of an image for day 28. The [...]

Published
2024
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2. CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target

Author

Le, Quy, Hadland, Brandon, Smith, Jenny L, Leonti, Amanda, Huang, Benjamin J, Ries, Rhonda, Hylkema, Tiffany A, Castro, Sommer, Tang, Thao T, McKay, Cyd N, Perkins, LaKeisha, Pardo, Laura, Sarthy, Jay, Beckman, Amy K, Williams, Robin, Idemmili, Rhonda, Furlan, Scott, Ishida, Takashi, Call, Lindsey, Srivastava, Shivani, Loeb, Anisha M, Milano, Filippo, Imren, Suzan, Morris, Shelli M, Pakiam, Fiona, Olson, James M, Loken, Michael R, Brodersen, Lisa Eidenschink, Riddell, Stanley R, Tarlock, Katherine, Bernstein, Irwin D, Loeb, Keith R, and Meshinchi, Soheil

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Pediatric Research Initiative, Pediatric, Cancer, Genetics, Pediatric Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Biotechnology, Hematology, Rare Diseases, Childhood Leukemia, Orphan Drug, 2.1 Biological and endogenous factors, Aetiology, Animals, Child, Child, Preschool, Humans, Infant, Disease Models, Animal, Folate Receptor 1, Immunotherapy, Adoptive, Leukemia, Megakaryoblastic, Acute, Oncogene Proteins, Fusion, T-Lymphocytes, Transcriptome, Xenograft Model Antitumor Assays, Cancer immunotherapy, Leukemias, Oncogenes, Oncology, Therapeutics, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem and progenitor cells (CB HSPCs) in an endothelial cell coculture system that recapitulates the transcriptome, morphology, and immunophenotype of C/G acute myeloid leukemia (AML) and induces highly aggressive leukemia in xenograft models. Interrogating the transcriptome of C/G-CB cells and primary C/G AML identified a library of C/G-fusion-specific genes that are potential targets for therapy. We developed chimeric antigen receptor (CAR) T cells directed against one of the targets, folate receptor α (FOLR1), and demonstrated their preclinical efficacy against C/G AML using in vitro and xenograft models. FOLR1 is also expressed in renal and pulmonary epithelium, raising concerns for toxicity that must be addressed for the clinical application of this therapy. Our findings underscore the role of the endothelial niche in promoting leukemic transformation of C/G-transduced CB HSPCs. Furthermore, this work has broad implications for studies of leukemogenesis applicable to a variety of oncogenic fusion-driven pediatric leukemias, providing a robust and tractable model system to characterize the molecular mechanisms of leukemogenesis and identify biomarkers for disease diagnosis and targets for therapy.

Published
2022

8. FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition

Author

Diab, Ahmed, Gem, Hakan, Swanger, Jherek, Kim, Hee Yeon, Smith, Kaleb, Zou, Grace, Raju, Sharat, Kao, Michael, Fitzgibbon, Matthew, Loeb, Keith R., Rodriguez, Cristina P., Méndez, Eduardo, Galloway, Denise A., Sidorova, Julia M., and Clurman, Bruce E.

Published
2020

9. CD74 is expressed in a subset of pediatric acute myeloid leukemia patients and is a promising target for therapy: a report from the Children’s Oncology Group

Author

Menssen, Andrew J., primary, Hudson, Chad A., additional, Alonzo, Todd, additional, Gerbing, Robert, additional, Pardo, Laura, additional, Leonti, Amanda, additional, Cook, Jacqueline A., additional, Hsu, Fan-Chi, additional, Lott, Loren L., additional, Dai, Fangyan, additional, Fearing, Collette, additional, Ghirardelli, Keely, additional, Hylkema, Tiffany, additional, Tarlock, Katherine, additional, Loeb, Keith R., additional, Kolb, Edward A., additional, Cooper, Todd, additional, Pollard, Jessica, additional, Wells, Denise A., additional, Loken, Michael R., additional, Aplenc, Richard, additional, Meshinchi, Soheil, additional, and Brodersen, Lisa Eidenschink, additional

Published
2024
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15. Preclinical studies targeting CD74 with STRO-001 antibody-drug conjugate in acute leukemia

Author

Le, Quy, primary, Tang, Thao, additional, Leonti, Amanda, additional, Castro, Sommer, additional, McKay, Cyd Nourigat, additional, Perkins, LaKeisha, additional, Pardo, Laura, additional, Kirkey, Danielle, additional, Hylkema, Tiffany, additional, Call, Lindsey, additional, Manselle, Makia, additional, Abrahams, Cristina, additional, Bedard, Kristin, additional, Molina, Arturo, additional, Brodersen, Lisa Eidenshinck, additional, Loken, Michael R., additional, Tarlock, Katherine, additional, Meshinchi, Soheil, additional, and Loeb, Keith R., additional

Published
2023
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16. Supplementary Figures from Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study

Author

Smith, Jenny L., primary, Ries, Rhonda E., primary, Hylkema, Tiffany, primary, Alonzo, Todd A., primary, Gerbing, Robert B., primary, Santaguida, Marianne T., primary, Eidenschink Brodersen, Lisa, primary, Pardo, Laura, primary, Cummings, Carrie L., primary, Loeb, Keith R., primary, Le, Quy, primary, Imren, Suzan, primary, Leonti, Amanda R., primary, Gamis, Alan S., primary, Aplenc, Richard, primary, Kolb, E. Anders, primary, Farrar, Jason E., primary, Triche, Timothy J., primary, Nguyen, Cu, primary, Meerzaman, Daoud, primary, Loken, Michael R., primary, Oehler, Vivian G., primary, Bolouri, Hamid, primary, and Meshinchi, Soheil, primary

Published
2023
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17. Supplementary Methods from Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study

Author

Smith, Jenny L., primary, Ries, Rhonda E., primary, Hylkema, Tiffany, primary, Alonzo, Todd A., primary, Gerbing, Robert B., primary, Santaguida, Marianne T., primary, Eidenschink Brodersen, Lisa, primary, Pardo, Laura, primary, Cummings, Carrie L., primary, Loeb, Keith R., primary, Le, Quy, primary, Imren, Suzan, primary, Leonti, Amanda R., primary, Gamis, Alan S., primary, Aplenc, Richard, primary, Kolb, E. Anders, primary, Farrar, Jason E., primary, Triche, Timothy J., primary, Nguyen, Cu, primary, Meerzaman, Daoud, primary, Loken, Michael R., primary, Oehler, Vivian G., primary, Bolouri, Hamid, primary, and Meshinchi, Soheil, primary

Published
2023
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18. Supplementary Tables from Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study

Author

Smith, Jenny L., primary, Ries, Rhonda E., primary, Hylkema, Tiffany, primary, Alonzo, Todd A., primary, Gerbing, Robert B., primary, Santaguida, Marianne T., primary, Eidenschink Brodersen, Lisa, primary, Pardo, Laura, primary, Cummings, Carrie L., primary, Loeb, Keith R., primary, Le, Quy, primary, Imren, Suzan, primary, Leonti, Amanda R., primary, Gamis, Alan S., primary, Aplenc, Richard, primary, Kolb, E. Anders, primary, Farrar, Jason E., primary, Triche, Timothy J., primary, Nguyen, Cu, primary, Meerzaman, Daoud, primary, Loken, Michael R., primary, Oehler, Vivian G., primary, Bolouri, Hamid, primary, and Meshinchi, Soheil, primary

Published
2023
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22. Targeting FOLR1 in high-risk CBF2AT3-GLIS2 pediatric AML with STRO-002 FOLR1–antibody-drug conjugate

Author

Tang, Thao, primary, Le, Quy, additional, Castro, Sommer, additional, Pardo, Laura, additional, McKay, Cyd Nourigat, additional, Perkins, LaKeisha, additional, Smith, Jenny, additional, Kirkey, Danielle, additional, Abrahams, Cristina, additional, Bedard, Kristin, additional, Molina, Arturo, additional, Brodersen, Lisa Eidenshinck, additional, Loken, Michael R., additional, Tarlock, Katherine, additional, Meshinchi, Soheil, additional, and Loeb, Keith R., additional

Published
2022
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23. Oncogenic role of a developmentally regulated NTRK2 splice variant

Author

Pattwell, Siobhan S., primary, Arora, Sonali, additional, Nuechterlein, Nicholas, additional, Zager, Michael, additional, Loeb, Keith R., additional, Cimino, Patrick J., additional, Holland, Nikolas C., additional, Reche-Ley, Noemi, additional, Bolouri, Hamid, additional, Almiron Bonnin, Damian A., additional, Szulzewsky, Frank, additional, Phadnis, Vaishnavi V., additional, Ozawa, Tatsuya, additional, Wagner, Michael J., additional, Haffner, Michael C., additional, Cao, Junyue, additional, Shendure, Jay, additional, and Holland, Eric C., additional

Published
2022
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28. Oncogenic role of a developmentally regulatedNTRK2splice variant

Author

Pattwell, Siobhan S., primary, Arora, Sonali, additional, Nuechterlein, Nicholas, additional, Zager, Michael, additional, Loeb, Keith R., additional, Cimino, Patrick J., additional, Holland, Nikolas C., additional, Reche-Ley, Noemi, additional, Bolouri, Hamid, additional, Almiron Bonnin, Damian A., additional, Szulzewsky, Frank, additional, Phadnis, Vaishnavi V., additional, Ozawa, Tatsuya, additional, Wagner, Michael J., additional, Haffner, Michael C., additional, Cao, Junyue, additional, Shendure, Jay, additional, and Holland, Eric C., additional

Published
2022
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30. Endothelial Cell Niche Promotes Leukemic Transformation of Human Cord Blood Stem/Progenitor Cells Expressing CBFA2T3-GLIS2 Oncogenic Fusion

Author

Le, Quy, primary, Hylkema, Tiffany A., additional, Castro, Sommer, additional, Smith, Jenny L., additional, Leonti, Amanda R., additional, Tang, Thao T., additional, Nourigat-Mckay, Cynthia, additional, Perkins, LaKeisha, additional, Pardo, Laura, additional, Eidenschink Brodersen, Lisa, additional, Loken, Michael R., additional, Ries, Rhonda E., additional, Loeb, Keith R., additional, and Meshinchi, Soheil, additional

Published
2021
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36. Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study

Author

Smith, Jenny L., primary, Ries, Rhonda E., additional, Hylkema, Tiffany, additional, Alonzo, Todd A., additional, Gerbing, Robert B., additional, Santaguida, Marianne T., additional, Eidenschink Brodersen, Lisa, additional, Pardo, Laura, additional, Cummings, Carrie L., additional, Loeb, Keith R., additional, Le, Quy, additional, Imren, Suzan, additional, Leonti, Amanda R., additional, Gamis, Alan S., additional, Aplenc, Richard, additional, Kolb, E. Anders, additional, Farrar, Jason E., additional, Triche, Timothy J., additional, Nguyen, Cu, additional, Meerzaman, Daoud, additional, Loken, Michael R., additional, Oehler, Vivian G., additional, Bolouri, Hamid, additional, and Meshinchi, Soheil, additional

Published
2020
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41. A high-resolution landscape of mutations in the BCL6 super-enhancer in normal human B cells.

Author

Jiang-Cheng Shen, Kamath-Loeb, Ashwini S., Kohrn, Brendan F., Loeb, Keith R., Preston, Bradley D., and Loeb, Lawrence A.

Subjects
B cells, DNA polymerases, GENE frequency
Abstract

The super-enhancers (SEs) of lineage-specific genes in B cells are off-target sites of somatic hypermutation. However, the inability to detect sufficient numbers of mutations in normal human B cells has precluded the generation of a high-resolution mutational landscape of SEs. Here we captured and sequenced 12 B cell SEs at single-nucleotide resolution from 10 healthy individuals across diverse ethnicities. We detected a total of approximately 9,000 subclonal mutations (allele frequencies <0.1%); of these, approximately 8,000 are present in the BCL6 SE alone. Within the BCL6 SE, we identified 3 regions of clustered mutations in which the mutation frequency is ∼7 × 10−4. Mutational spectra show a predominance of C > T/G > A and A > G/T > C substitutions, consistent with the activities of activation-induced-cytidine deaminase (AID) and the A-T mutator, DNA polymerase η, respectively, in mutagenesis in normal B cells. Analyses of mutational signatures further corroborate the participation of these factors in this process. Single base substitution signatures SBS85, SBS37, and SBS39 were found in the BCL6 SE. While SBS85 is a denoted signature of AID in lymphoid cells, the etiologies of SBS37 and SBS39 are unknown. Our analysis suggests the contribution of error-prone DNA polymerases to the latter signatures. The high-resolution mutation landscape has enabled accurate profiling of subclonal mutations in B cell SEs in normal individuals. By virtue of the fact that subclonal SE mutations are clonally expanded in B cell lymphomas, our studies also offer the potential for early detection of neoplastic alterations. [ABSTRACT FROM AUTHOR]

Published
2019
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43. Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo

Author

Minella, Alex C., Loeb, Keith R., Knecht, Andrea, Welcker, Markus, Varnum-Finney, Barbara J., Bernstein, Irwin D., Roberts, James M., and Clurman, Bruce E.

Subjects
Phosphorylation -- Analysis, Alanine -- Chemical properties, Gene mutations -- Analysis, Genetically modified mice -- Research, Threonine -- Chemical properties, Biological sciences
Abstract

The construction of a knockin mouse in which both N- and C-terminal degrons were mutated by threonine to alanine substitutions and regulation of cyclin E by Fbw7 abolished by ablation of both degrons is reported. The result data provide insight into the critical role of both degrons in regulating cyclin E activity and complete loss of Fbw7-mediated cyclin E degradation that causes spontaneous and cell type-specific proliferative anomalies.

Published
2008

45. Massively parallel digital transcriptional profiling of single cells

Author

Zheng, Grace X. Y., primary, Terry, Jessica M., additional, Belgrader, Phillip, additional, Ryvkin, Paul, additional, Bent, Zachary W., additional, Wilson, Ryan, additional, Ziraldo, Solongo B., additional, Wheeler, Tobias D., additional, McDermott, Geoff P., additional, Zhu, Junjie, additional, Gregory, Mark T., additional, Shuga, Joe, additional, Montesclaros, Luz, additional, Underwood, Jason G., additional, Masquelier, Donald A., additional, Nishimura, Stefanie Y., additional, Schnall-Levin, Michael, additional, Wyatt, Paul W., additional, Hindson, Christopher M., additional, Bharadwaj, Rajiv, additional, Wong, Alexander, additional, Ness, Kevin D., additional, Beppu, Lan W., additional, Deeg, H. Joachim, additional, McFarland, Christopher, additional, Loeb, Keith R., additional, Valente, William J., additional, Ericson, Nolan G., additional, Stevens, Emily A., additional, Radich, Jerald P., additional, Mikkelsen, Tarjei S., additional, Hindson, Benjamin J., additional, and Bielas, Jason H., additional

Published
2017
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47. Potent and Target Specific Cytotoxicity of PRAME TCR Mimic CAR T Cells in KMT2A-Rearranged AML Patient-Derived Xenograft Model

Author

Kirkey, Danielle C, Robinson, Leila, Hylkema, Tiffany, Loeb, Anisha, Ries, Rhonda E, McKay, Cyd, Root, Christina, Pardo, Laura, Loeb, Keith R., Le, Quy, Scheinberg, David A., and Meshinchi, Soheil

Abstract

Chimeric antigen receptor (CAR) T cell therapy was a resounding success in CD19+ ALL despite the fact that it is essential for B-cell maturation because it is not expressed during normal myeloid hematopoiesis. Normal and leukemic B-cells are targeted by CD19+ CAR T-cells without causing myeloid hematopoietic toxicity. Advancing such therapy to acute myeloid leukemia (AML) has been challenging in part due to a paucity of “dispensable” targets or targets whose expression is limited to the leukemic cells. Using a large AML and normal hematopoiesis transcriptome database, we pursued discovery of “AML-Restricted Targets”; genes that are silent in normal hematopoiesis but expressed in AML. This broad discovery effort yielded a library of AML-restricted targets that included PRAME (Preferentially Expressed Antigen in Melanoma), an intracellular protein expressed via MHC on the cell surface, to be a highly expressed in AML including the aggressive KMT2A-rearranged (KMT2A-r) AML. We used a TCR mimic (mTCR) antibody, which recognizes the PRAME peptide/HLA-A2 complex on the tumor cell surface, to develop a PRAME directed TCR mimic CAR T (PRAME mTCRCAR T) for pre-clinical studies. Studies in cell lines and CDX models have shown significant efficacy of this CAR T (Kirkey, Bld Adv. 2022). To conduct final IND-enabling studies, we generated a KMT2A-r HLA-A2+/PRAME+ patient-derived xenograft (PDX) model to treat with PRAME mTCRCAR T-cells. Here we demonstrate the in vivoactivity of PRAME mTCRCAR T cells against this unique PDX AML model. VL and VH sequences from the PRAME specific TCR mimic antibody (Pr20) were used to construct the single-chain fragment variable domain into the 41-BB/CD3ζ CAR vector. The PDX model was derived from a PRAME +/HLA-A2 +pediatric patient with KMTA2-r AML. PDX cells were transduced with lentiviral ffluciferase for noninvasive bioluminescent IVIS imaging to monitor leukemic progression. Mice were transplanted with 1x10 6PDX leukemia cells then 1 week later, PDX leukemia-bearing mice were treated with unmodified T cells or PRAME mTCRCAR T cells at 5x10 6cells (1:1 CD4:CD8) per mouse. Leukemia burden was measured by IVIS imaging and regular peripheral blood analysis.

Published
2023
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48. Massively parallel digital transcriptional profiling of single cells

Author

Zheng, Grace X.Y., primary, Terry, Jessica M., additional, Belgrader, Phillip, additional, Ryvkin, Paul, additional, Bent, Zachary W., additional, Wilson, Ryan, additional, Ziraldo, Solongo B., additional, Wheeler, Tobias D., additional, McDermott, Geoff P., additional, Zhu, Junjie, additional, Gregory, Mark T., additional, Shuga, Joe, additional, Montesclaros, Luz, additional, Masquelier, Donald A., additional, Nishimura, Stefanie Y., additional, Schnall-Levin, Michael, additional, Wyatt, Paul W, additional, Hindson, Christopher M., additional, Bharadwaj, Rajiv, additional, Wong, Alexander, additional, Ness, Kevin D., additional, Beppu, Lan W., additional, Deeg, H. Joachim, additional, McFarland, Christopher, additional, Loeb, Keith R., additional, Valente, William J., additional, Ericson, Nolan G., additional, Stevens, Emily A., additional, Radich, Jerald P., additional, Mikkelsen, Tarjei S., additional, Hindson, Benjamin J., additional, and Bielas, Jason H., additional

Published
2016
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