Search

Your search keyword '"Majeti, Ravindra"' showing total 787 results
Start Over Author "Majeti, Ravindra" Publication Year Range Last 50 years
787 results on '"Majeti, Ravindra"'

1. Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells

Author

Fowler, Jonas L, Zheng, Sherry Li, Nguyen, Alana, Chen, Angela, Xiong, Xiaochen, Chai, Timothy, Chen, Julie Y, Karigane, Daiki, Banuelos, Allison M, Niizuma, Kouta, Kayamori, Kensuke, Nishimura, Toshinobu, Cromer, M Kyle, Gonzalez-Perez, David, Mason, Charlotte, Liu, Daniel Dan, Yilmaz, Leyla, Miquerol, Lucile, Porteus, Matthew H, Luca, Vincent C, Majeti, Ravindra, Nakauchi, Hiromitsu, Red-Horse, Kristy, Weissman, Irving L, Ang, Lay Teng, and Loh, Kyle M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research, Regenerative Medicine, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Transplantation, Hematology, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Stem Cell Research - Embryonic - Human, Underpinning research, 1.1 Normal biological development and functioning, Blood, Animals, Humans, Mice, Cell Differentiation, Cell Lineage, Endothelial Cells, Hematopoiesis, Hematopoietic Stem Cells, Homeodomain Proteins, Pluripotent Stem Cells, Transcription Factors, Basic-Leucine Zipper Transcription Factors, artery, developmental biology, hematopoietic stem cell, human pluripotent stem cell differentiation, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract

The developmental origin of blood-forming hematopoietic stem cells (HSCs) is a longstanding question. Here, our non-invasive genetic lineage tracing in mouse embryos pinpoints that artery endothelial cells generate HSCs. Arteries are transiently competent to generate HSCs for 2.5 days (∼E8.5-E11) but subsequently cease, delimiting a narrow time frame for HSC formation in vivo. Guided by the arterial origins of blood, we efficiently and rapidly differentiate human pluripotent stem cells (hPSCs) into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and >90% pure hematopoietic progenitors within 10 days. hPSC-derived hematopoietic progenitors generate T, B, NK, erythroid, and myeloid cells in vitro and, critically, express hallmark HSC transcription factors HLF and HOXA5-HOXA10, which were previously challenging to upregulate. We differentiated hPSCs into highly enriched HLF+ HOXA+ hematopoietic progenitors with near-stoichiometric efficiency by blocking formation of unwanted lineages at each differentiation step. hPSC-derived HLF+ HOXA+ hematopoietic progenitors could avail both basic research and cellular therapies.

Published
2024

5. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication

Author

Theruvath, Johanna, Menard, Marie, Smith, Benjamin AH, Linde, Miles H, Coles, Garry L, Dalton, Guillermo Nicolas, Wu, Wei, Kiru, Louise, Delaidelli, Alberto, Sotillo, Elena, Silberstein, John L, Geraghty, Anna C, Banuelos, Allison, Radosevich, Molly Thomas, Dhingra, Shaurya, Heitzeneder, Sabine, Tousley, Aidan, Lattin, John, Xu, Peng, Huang, Jing, Nasholm, Nicole, He, Andy, Kuo, Tracy C, Sangalang, Emma RB, Pons, Jaume, Barkal, Amira, Brewer, Rachel E, Marjon, Kristopher D, Vilches-Moure, Jose G, Marshall, Payton L, Fernandes, Ricardo, Monje, Michelle, Cochran, Jennifer R, Sorensen, Poul H, Daldrup-Link, Heike E, Weissman, Irving L, Sage, Julien, Majeti, Ravindra, Bertozzi, Carolyn R, Weiss, William A, Mackall, Crystal L, and Majzner, Robbie G

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Pediatric Research Initiative, Pediatric, Neurosciences, Pediatric Cancer, Rare Diseases, Orphan Drug, Cancer, Neuroblastoma, Animals, Bone Neoplasms, CD47 Antigen, Cell Line, Tumor, Humans, Immunotherapy, Mice, Neoplasm Recurrence, Local, Phagocytosis, Tumor Microenvironment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

The disialoganglioside GD2 is overexpressed on several solid tumors, and monoclonal antibodies targeting GD2 have substantially improved outcomes for children with high-risk neuroblastoma. However, approximately 40% of patients with neuroblastoma still relapse, and anti-GD2 has not mediated significant clinical activity in any other GD2+ malignancy. Macrophages are important mediators of anti-tumor immunity, but tumors resist macrophage phagocytosis through expression of the checkpoint molecule CD47, a so-called 'Don't eat me' signal. In this study, we establish potent synergy for the combination of anti-GD2 and anti-CD47 in syngeneic and xenograft mouse models of neuroblastoma, where the combination eradicates tumors, as well as osteosarcoma and small-cell lung cancer, where the combination significantly reduces tumor burden and extends survival. This synergy is driven by two GD2-specific factors that reorient the balance of macrophage activity. Ligation of GD2 on tumor cells (a) causes upregulation of surface calreticulin, a pro-phagocytic 'Eat me' signal that primes cells for removal and (b) interrupts the interaction of GD2 with its newly identified ligand, the inhibitory immunoreceptor Siglec-7. This work credentials the combination of anti-GD2 and anti-CD47 for clinical translation and suggests that CD47 blockade will be most efficacious in combination with monoclonal antibodies that alter additional pro- and anti-phagocytic signals within the tumor microenvironment.

Published
2022

6. Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency

Author

Pavel-Dinu, Mara, Gardner, Cameron L., Nakauchi, Yusuke, Kawai, Tomoki, Delmonte, Ottavia M., Palterer, Boaz, Bosticardo, Marita, Pala, Francesca, Viel, Sebastien, Malech, Harry L., Ghanim, Hana Y., Bode, Nicole M., Kurgan, Gavin L., Detweiler, Angela M., Vakulskas, Christopher A., Neff, Norma F., Sheikali, Adam, Menezes, Sherah T., Chrobok, Jade, Hernández González, Elaine M., Majeti, Ravindra, Notarangelo, Luigi D., and Porteus, Matthew H.

Published
2024
Full Text
View/download PDF

7. Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes—Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes

Author

Aakash, Fnu, Gisriel, Savanah D., Zeidan, Amer M., Bennett, John M., Bejar, Rafael, Bewersdorf, Jan Philipp, Borate, Uma M., Boultwood, Jacqueline, Brunner, Andrew M., Buckstein, Rena, Carraway, Hetty, Churpek, Jane E., Daver, Naval G., DeZern, Amy E., Efficace, Fabio, Fenaux, Pierre, Figueroa, Maria E., Garcia-Manero, Guillero, Gore, Steven D., Greenberg, Peter L., Griffiths, Elizabeth A., Halene, Stephanie, Hourigan, Christopher S., Kim, Tae Kon, Kim, Nina, Komrokji, Rami S., Kutchroo, Vijay, List, Alan F., Little, Richard F., Majeti, Ravindra, Nazha, Aziz, Nimer, Stephen D., Odenike, Olatoyosi, Padron, Eric, Patnaik, Mrinal M., Platzbecker, Uwe, Della Porta, Matteo G., Roboz, Gail J., Sallman, David A., Santini, Valeria, Sanz, Guillermo, Savona, Michael R., Sekeres, Mikkael A., Stahl, Maximilian, Starczynowski, Daniel T., Steensma, David P., Taylor, Justin, Abdel-Wahab, Omer, Wei, Andrew H., Zhuoer, Xie, Xu, Mina L., Hasserjian, Robert P., and Loghavi, Sanam

Published
2024
Full Text
View/download PDF

8. Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells

Author

Cromer, M Kyle, Camarena, Joab, Martin, Renata M, Lesch, Benjamin J, Vakulskas, Christopher A, Bode, Nicole M, Kurgan, Gavin, Collingwood, Michael A, Rettig, Garrett R, Behlke, Mark A, Lemgart, Viktor T, Zhang, Yankai, Goyal, Ankush, Zhao, Feifei, Ponce, Ezequiel, Srifa, Waracharee, Bak, Rasmus O, Uchida, Naoya, Majeti, Ravindra, Sheehan, Vivien A, Tisdale, John F, Dever, Daniel P, and Porteus, Matthew H

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Stem Cell Research, Cooley's Anemia, Orphan Drug, Regenerative Medicine, Biotechnology, Genetics, Stem Cell Research - Nonembryonic - Human, Hematology, Gene Therapy, Stem Cell Research - Nonembryonic - Non-Human, Rare Diseases, Transplantation, 5.2 Cellular and gene therapies, Blood, Anemia, Sickle Cell, Animals, Antigens, CD34, Dependovirus, Erythrocytes, Gene Editing, Genes, Reporter, Genetic Loci, Genetic Therapy, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Hemoglobins, Humans, Mice, Promoter Regions, Genetic, alpha-Globins, beta-Globins, beta-Thalassemia, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

β-Thalassemia pathology is due not only to loss of β-globin (HBB), but also to erythrotoxic accumulation and aggregation of the β-globin-binding partner, α-globin (HBA1/2). Here we describe a Cas9/AAV6-mediated genome editing strategy that can replace the entire HBA1 gene with a full-length HBB transgene in β-thalassemia-derived hematopoietic stem and progenitor cells (HSPCs), which is sufficient to normalize β-globin:α-globin messenger RNA and protein ratios and restore functional adult hemoglobin tetramers in patient-derived red blood cells. Edited HSPCs were capable of long-term and bilineage hematopoietic reconstitution in mice, establishing proof of concept for replacement of HBA1 with HBB as a novel therapeutic strategy for curing β-thalassemia.

Published
2021

9. Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)

Author

Bewersdorf, Jan Philipp, Xie, Zhuoer, Bejar, Rafael, Borate, Uma, Boultwood, Jacqueline, Brunner, Andrew M., Buckstein, Rena, Carraway, Hetty E., Churpek, Jane E., Daver, Naval G., Porta, Matteo Giovanni Della, DeZern, Amy E., Fenaux, Pierre, Figueroa, Maria E., Gore, Steven D., Griffiths, Elizabeth A., Halene, Stephanie, Hasserjian, Robert P., Hourigan, Christopher S., Kim, Tae Kon, Komrokji, Rami, Kuchroo, Vijay K., List, Alan F., Loghavi, Sanam, Majeti, Ravindra, Odenike, Olatoyosi, Patnaik, Mrinal M., Platzbecker, Uwe, Roboz, Gail J., Sallman, David A., Santini, Valeria, Sanz, Guillermo, Sekeres, Mikkael A., Stahl, Maximilian, Starczynowski, Daniel T., Steensma, David P., Taylor, Justin, Abdel-Wahab, Omar, Xu, Mina L., Savona, Michael R., Wei, Andrew H., and Zeidan, Amer M.

Published
2023
Full Text
View/download PDF

10. Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1

Author

Mabe, Nathaniel W., Huang, Min, Dalton, Guillermo N., Alexe, Gabriela, Schaefer, Daniel A., Geraghty, Anna C., Robichaud, Amanda L., Conway, Amy S., Khalid, Delan, Mader, Marius M., Belk, Julia A., Ross, Kenneth N., Sheffer, Michal, Linde, Miles H., Ly, Nghi, Yao, Winnie, Rotiroti, Maria Caterina, Smith, Benjamin A. H., Wernig, Marius, Bertozzi, Carolyn R., Monje, Michelle, Mitsiades, Constantine S., Majeti, Ravindra, Satpathy, Ansuman T., Stegmaier, Kimberly, and Majzner, Robbie G.

Published
2022
Full Text
View/download PDF

12. A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

Author

Ediriwickrema, Asiri, primary, Nakauchi, Yusuke, additional, Fan, Amy, additional, Köhnke, Thomas, additional, Hu, Xiaoyi, additional, Luca, Bogdan A, additional, Kim, YeEun, additional, Ramakrishnan, Sreejith, additional, Nakamoto, Margaret, additional, Karigane, Daiki, additional, Linde, Miles H, additional, Azizi, Armon, additional, Newman, Aaron M, additional, Gentles, Andrew J, additional, and Majeti, Ravindra, additional

Published
2024
Full Text
View/download PDF

16. Author Correction: Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia

Author

Bassal, Mahmoud A., Samaraweera, Saumya E., Lim, Kelly, Benard, Brooks A., Bailey, Sheree, Kaur, Satinder, Leo, Paul, Toubia, John, Thompson-Peach, Chloe, Nguyen, Tran, Maung, Kyaw Ze Ya, Casolari, Debora A., Iarossi, Diana G., Pagani, Ilaria S., Powell, Jason, Pitson, Stuart, Natera, Siria, Roessner, Ute, Lewis, Ian D., Brown, Anna L., Tenen, Daniel G., Robinson, Nirmal, Ross, David M., Majeti, Ravindra, Gonda, Thomas J., Thomas, Daniel, and D’Andrea, Richard J.

Published
2022
Full Text
View/download PDF

18. Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia

Author

Bassal, Mahmoud A., Samaraweera, Saumya E., Lim, Kelly, Benard, Brooks A., Bailey, Sheree, Kaur, Satinder, Leo, Paul, Toubia, John, Thompson-Peach, Chloe, Nguyen, Tran, Maung, Kyaw Ze Ya, Casolari, Debora A., Iarossi, Diana G., Pagani, Ilaria S., Powell, Jason, Pitson, Stuart, Natera, Siria, Roessner, Ute, Lewis, Ian D., Brown, Anna L., Tenen, Daniel G., Robinson, Nirmal, Ross, David M., Majeti, Ravindra, Gonda, Thomas J., Thomas, Daniel, and D’Andrea, Richard J.

Published
2022
Full Text
View/download PDF

19. Identification of the Human Skeletal Stem Cell

Author

Chan, Charles KF, Gulati, Gunsagar S, Sinha, Rahul, Tompkins, Justin Vincent, Lopez, Michael, Carter, Ava C, Ransom, Ryan C, Reinisch, Andreas, Wearda, Taylor, Murphy, Matthew, Brewer, Rachel E, Koepke, Lauren S, Marecic, Owen, Manjunath, Anoop, Seo, Eun Young, Leavitt, Tripp, Lu, Wan-Jin, Nguyen, Allison, Conley, Stephanie D, Salhotra, Ankit, Ambrosi, Thomas H, Borrelli, Mimi R, Siebel, Taylor, Chan, Karen, Schallmoser, Katharina, Seita, Jun, Sahoo, Debashis, Goodnough, Henry, Bishop, Julius, Gardner, Michael, Majeti, Ravindra, Wan, Derrick C, Goodman, Stuart, Weissman, Irving L, Chang, Howard Y, and Longaker, Michael T

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Regenerative Medicine, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Transplantation, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Genetics, Stem Cell Research - Nonembryonic - Non-Human, Aetiology, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Musculoskeletal, Animals, Bone Development, Bone and Bones, Cartilage, Cell Differentiation, Hematopoietic Stem Cells, Humans, Induced Pluripotent Stem Cells, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Signal Transduction, Single-Cell Analysis, Stem Cells, Stromal Cells, Transcriptome, ATAC-sequencing, HSC, and stromal progenitor, bone, bone fracture repair, bone marrow niche, cartilage, human skeletal stem cell, single cell RNA-sequencing, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

Published
2018

27. Alkylator-Induced and Patient-Derived Xenograft Mouse Models of Therapy-Related Myeloid Neoplasms Model Clinical Disease and Suggest the Presence of Multiple Cell Subpopulations with Leukemia Stem Cell Activity.

Author

Jonas, Brian A, Johnson, Carl, Gratzinger, Dita, and Majeti, Ravindra

Subjects
Bone Marrow Cells, Animals, Humans, Mice, Neoplasms, Second Primary, Myelodysplastic Syndromes, Disease Models, Animal, Ethylnitrosourea, Alkylating Agents, Neoplastic Stem Cells, Leukemia, Myeloid, Acute, General Science & Technology
Abstract

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive bone marrow cancers arising from transformed hematopoietic stem and progenitor cells (HSPC). Therapy-related AML and MDS (t-AML/MDS) comprise a subset of AML cases occurring after exposure to alkylating chemotherapy and/or radiation and are associated with a very poor prognosis. Less is known about the pathogenesis and disease-initiating/leukemia stem cell (LSC) subpopulations of t-AML/MDS compared to their de novo counterparts. Here, we report the development of mouse models of t-AML/MDS. First, we modeled alkylator-induced t-AML/MDS by exposing wild type adult mice to N-ethyl-N-nitrosurea (ENU), resulting in several models of AML and MDS that have clinical and pathologic characteristics consistent with human t-AML/MDS including cytopenia, myelodysplasia, and shortened overall survival. These models were limited by their inability to transplant clinically aggressive disease. Second, we established three patient-derived xenograft models of human t-AML. These models led to rapidly fatal disease in recipient immunodeficient xenografted mice. LSC activity was identified in multiple HSPC subpopulations suggesting there is no canonical LSC immunophenotype in human t-AML. Overall, we report several new t-AML/MDS mouse models that could potentially be used to further define disease pathogenesis and test novel therapeutics.

Published
2016

30. Supplementary Figures S1-S13 from Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells

Author

Nelde, Annika, primary, Schuster, Heiko, primary, Heitmann, Jonas S., primary, Bauer, Jens, primary, Maringer, Yacine, primary, Zwick, Melissa, primary, Volkmer, Jens-Peter, primary, Chen, James Y., primary, Stanger, Anna M. Paczulla, primary, Lehmann, Ariane, primary, Appiah, Bismark, primary, Märklin, Melanie, primary, Rücker-Braun, Elke, primary, Salih, Helmut R., primary, Roerden, Malte, primary, Schroeder, Sarah M., primary, Häring, Max-Felix, primary, Schlosser, Andreas, primary, Schetelig, Johannes, primary, Schmitz, Marc, primary, Boerries, Melanie, primary, Köhler, Natalie, primary, Lengerke, Claudia, primary, Majeti, Ravindra, primary, Weissman, Irving L., primary, Rammensee, Hans-Georg, primary, and Walz, Juliane S., primary

Published
2023
Full Text
View/download PDF

31. Data from Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells

Author

Nelde, Annika, primary, Schuster, Heiko, primary, Heitmann, Jonas S., primary, Bauer, Jens, primary, Maringer, Yacine, primary, Zwick, Melissa, primary, Volkmer, Jens-Peter, primary, Chen, James Y., primary, Stanger, Anna M. Paczulla, primary, Lehmann, Ariane, primary, Appiah, Bismark, primary, Märklin, Melanie, primary, Rücker-Braun, Elke, primary, Salih, Helmut R., primary, Roerden, Malte, primary, Schroeder, Sarah M., primary, Häring, Max-Felix, primary, Schlosser, Andreas, primary, Schetelig, Johannes, primary, Schmitz, Marc, primary, Boerries, Melanie, primary, Köhler, Natalie, primary, Lengerke, Claudia, primary, Majeti, Ravindra, primary, Weissman, Irving L., primary, Rammensee, Hans-Georg, primary, and Walz, Juliane S., primary

Published
2023
Full Text
View/download PDF

32. Supplementary Tables S1 to S15 from Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells

Author

Nelde, Annika, primary, Schuster, Heiko, primary, Heitmann, Jonas S., primary, Bauer, Jens, primary, Maringer, Yacine, primary, Zwick, Melissa, primary, Volkmer, Jens-Peter, primary, Chen, James Y., primary, Stanger, Anna M. Paczulla, primary, Lehmann, Ariane, primary, Appiah, Bismark, primary, Märklin, Melanie, primary, Rücker-Braun, Elke, primary, Salih, Helmut R., primary, Roerden, Malte, primary, Schroeder, Sarah M., primary, Häring, Max-Felix, primary, Schlosser, Andreas, primary, Schetelig, Johannes, primary, Schmitz, Marc, primary, Boerries, Melanie, primary, Köhler, Natalie, primary, Lengerke, Claudia, primary, Majeti, Ravindra, primary, Weissman, Irving L., primary, Rammensee, Hans-Georg, primary, and Walz, Juliane S., primary

Published
2023
Full Text
View/download PDF

37. Enasidenib drives human erythroid differentiation independently of isocitrate dehydrogenase 2

Author

Dutta, Ritika, Zhang, Tian Yi, Kohnke, Thomas, Thomas, Daniel, Linde, Miles, Gars, Eric, Stafford, Melissa, Kaur, Satinder, Nakauchi, Yusuke, Yin, Raymond, Azizi, Armon, Narla, Anupama, and Majeti, Ravindra

Subjects
Venetoclax, Enasidenib, Heme, Hemoglobins, Hematopoietic stem cells, Medical research, Anemia -- Care and treatment, Stem cells, Glycosylated hemoglobin, Acute myelocytic leukemia, Medical economics, Clinical trials, Myeloid leukemia, Diseases, Morbidity, Cancer patients, Health care industry
Abstract

Cancer-related anemia is present in more than 60% of newly diagnosed cancer patients and is associated with substantial morbidity and high medical costs. Drugs that enhance erythropoiesis are urgently required to decrease transfusion rates and improve quality of life. Clinical studies have observed an unexpected improvement in hemoglobin and RBC transfusionindependence in patients with acute myeloid leukemia (AML) treated with the isocitrate dehydrogenase 2 (IDH2) mutantspecific inhibitor enasidenib, leading to improved quality of life without a reduction in AML disease burden. Here, we demonstrate that enasidenib enhanced human erythroid differentiation of hematopoietic progenitors. The phenomenon was not observed with other IDH1/2 inhibitors and occurred in IDH2-deficient CRISPR-engineered progenitors independently of D-2-hydroxyglutarate. The effect of enasidenib on hematopoietic progenitors was mediated by protoporphyrin accumulation, driving heme production and erythroid differentiation in committed [CD71.sup.+] progenitors rather than hematopoietic stem cells. Our results position enasidenib as a promising therapeutic agent for improvement of anemia and provide the basis for a clinical trial using enasidenib to decrease transfusion dependence in a wide array of clinical contexts., Introduction Acute myeloid leukemia (AML) remains one of the most difficult cancers to treat, with a low cure rate (~25%) and a 5-year survival rate of 28% (1, 2). High-throughput [...]

Published
2020
Full Text
View/download PDF

44. Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells

Author

Nelde, Annika, primary, Schuster, Heiko, additional, Heitmann, Jonas S., additional, Bauer, Jens, additional, Maringer, Yacine, additional, Zwick, Melissa, additional, Volkmer, Jens-Peter, additional, Chen, James Y., additional, Stanger, Anna M. Paczulla, additional, Lehmann, Ariane, additional, Appiah, Bismark, additional, Märklin, Melanie, additional, Rücker-Braun, Elke, additional, Salih, Helmut R., additional, Roerden, Malte, additional, Schroeder, Sarah M., additional, Häring, Max-Felix, additional, Schlosser, Andreas, additional, Schetelig, Johannes, additional, Schmitz, Marc, additional, Boerries, Melanie, additional, Köhler, Natalie, additional, Lengerke, Claudia, additional, Majeti, Ravindra, additional, Weissman, Irving L., additional, Rammensee, Hans-Georg, additional, and Walz, Juliane S., additional

Published
2023
Full Text
View/download PDF

46. RUNX1 loss renders hematopoietic and leukemic cells dependent on interleukin-3 and sensitive to JAK inhibition

Author

Fan, Amy C., primary, Nakauchi, Yusuke, additional, Bai, Lawrence, additional, Azizi, Armon, additional, Nuno, Kevin A., additional, Zhao, Feifei, additional, Köhnke, Thomas, additional, Karigane, Daiki, additional, Cruz-Hernandez, David, additional, Reinisch, Andreas, additional, Khatri, Purvesh, additional, and Majeti, Ravindra, additional

Published
2023
Full Text
View/download PDF

50. Supplementary Tables 1-6 from Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia

Author

Kotini, Andriana G., primary, Carcamo, Saul, primary, Cruz-Rodriguez, Nataly, primary, Olszewska, Malgorzata, primary, Wang, Tiansu, primary, Demircioglu, Deniz, primary, Chang, Chan-Jung, primary, Bernard, Elsa, primary, Chao, Mark P., primary, Majeti, Ravindra, primary, Luo, Hanzhi, primary, Kharas, Michael G., primary, Hasson, Dan, primary, and Papapetrou, Eirini P., primary

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results