Novel therapeutic approach to improve hematopoiesis in low risk MDS by targeting MDSCs with the Fc-engineered CD33 antibody BI 836858
Open accessAbstract
We recently reported that the accumulation of myeloid-derived suppressor cells (MDSC), defined as CD33+HLA-DR-Lin-, has a direct role in the pathogenesis of myelodysplastic syndrome (MDS). In particular, CD33 is strongly expressed in MDSC isolated from patients with MDS where it has an important role in MDSC-mediated hematopoietic suppressive function through its activation by S100A9. Therefore, we tested whether blocking this interaction with a fully human, Fc-engineered monoclonal antibody against CD33 (BI 836858) suppresses CD33-mediated signal transduction and improves the bone marrow microenvironment in MDS. We observed that BI 836858 can reduce MDSC by antibody-dependent cellular cytotoxicity, which correlated with increases in granule mobilization and cell death. BI 836858 can also block CD33 downstream signaling preventing immune-suppressive cytokine secretion, which correlates with a significant increase in the formation of CFU-GM and BFU-E colonies. Activation of the CD33 pathway can cause reactive oxygen species (ROS)-induced genomic instability but BI 836858 reduced both ROS and the levels of double strand breaks and adducts (measured by comet assay and γH2AX). This work provides the ground for the development of a novel group of therapies for MDS aimed at MDSC and their disease-promoting properties with the goal of improving hematopoiesis in patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
MDSCs are sufficient to create an MDS phenotype in murine experiments, and targeting them or their expansion leads to reconstitution of normal hematopoiesis.
“MDSCs are sufficient to create an MDS phenotype in murine experiments, and targeting them or their expansion leads to reconstitution of normal hematopoiesis.76,77”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [77]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
Myeloid-derived-suppressor cells as regulators of the immune system
Gabrilovich, D. I., & Nagaraj, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2506 · Cited by 6,753 · see citing works
Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · see citing works
Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion
List, A., Dewald, G., Bennett, J., Giagounidis, A., Raza, A., Feldman, E., Powell, B., Greenberg, P., Thomas, D., Stone, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061292 · Cited by 1,319 · see citing works
Self-citationGamma-H2AX - a novel biomarker for DNA double-strand breaks.
Kuo, L. J., & Yang, L. (2008) · PubMed · Cited by 1,173 · see citing works
History of myeloid-derived suppressor cells
Talmadge, J. E., & Gabrilovich, D. I. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3581 · Cited by 1,148 · see citing works
Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., et al. (2010) · Nature · doi:10.1038/nature08851 · Cited by 1,115 · see citing works
Efficacy of Lenalidomide in Myelodysplastic Syndromes
List, A., Kurtin, S., Roe, D. J., Buresh, A., Mahadevan, D., Fuchs, D., Rimsza, L., Heaton, R., Knight, R., & Zeldis, J. B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa041668 · Cited by 880 · see citing works
Self-citationEhrchen, J. M., Sunderkötter, C. H., Foell, D., Vogl, T., & Roth, J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1008647 · Cited by 848 · see citing works
Hills, R. K., Castaigné, S., Appelbaum, F. R., Delaunay, J., Petersdorf, S. H., Othus, M. K. D., Estey, E. H., Dombret, H., Chevret, S., Ifrah, N., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70281-5 · Cited by 722 · see citing works
The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype
Basiorka, A. A., McGraw, K. L., Eksioglu, E. A., Chen, X., Johnson, J., Zhang, L., Zhang, Q., Irvine, B. A., Cluzeau, T., Sallman, D. A., et al. (2016) · Blood · doi:10.1182/blood-2016-07-730556 · Cited by 356 · see citing works
Self-citationRole Of Immature Myeloid Cells in Mechanisms of Immune Evasion In Cancer
Kusmartsev, S. A., & Gabrilovich, D. I. (2005) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0048-z · Cited by 346 · see citing works
Nimer, S. D. (2008) · Blood · doi:10.1182/blood-2007-08-078139 · Cited by 337 · see citing works
Induction of myelodysplasia by myeloid-derived suppressor cells
Chen, X., Eksioglu, E. A., Zhou, J., Zhang, L., Djeu, J., Fortenbery, N., Epling-Burnette, P., Van Bijnen, S., Dolstra, H., Cannon, J., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67580 · Cited by 316 · see citing works
Self-citationSade-Feldman, M., Kanterman, J., Ish‐Shalom, E., Elnekave, M., Horwitz, E. P., & Baniyash, M. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.007 · Cited by 306 · see citing works
Kristinsson, S. Y., Björkholm, M., Hultcrantz, M. L., Derolf, Å. R., Landgren, O., & Goldin, L. R. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.8540 · Cited by 288 · see citing works
Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients
Estey, E. H. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.2731 · Cited by 235 · see citing works
Epling‐Burnette, P. K., Bai, F., Painter, J. S., Rollison, D. E. M., Salih, H. R., Krusch, M., Zou, J., Ku, E., Zhong, B., Boulware, D. C., et al. (2007) · Blood · doi:10.1182/blood-2006-07-035519 · Cited by 232 · see citing works
Self-citationLarson, R. A., Boogaerts, M. A., Estey, E. H., Karanes, C., Stadtmauer, E. A., Sievers, E. L., Mineur, P., Bennett, J. M., Berger, M. S., Eten, C. B., et al. (2002) · Leukemia · doi:10.1038/sj.leu.2402677 · Cited by 221 · see citing works
Paul, S. P., Taylor, L. S., Stansbury, E. K., & McVicar, D. W. (2000) · Blood · doi:10.1182/blood.v96.2.483 · Cited by 204 · see citing works
Paul, S. P., Taylor, L. S., Stansbury, E. K., & McVicar, D. W. (2000) · Blood · doi:10.1182/blood.v96.2.483.014k40_483_490 · Cited by 202 · see citing works
Sheng, W., Chen, X., Rocha, K., Epling‐Burnette, P. K., Djeu, J. Y., Liu, Q., Byrd, J. C., Sokol, L., Lawrence, N., Pireddu, R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811267106 · Cited by 192 · see citing works
Self-citationTaylor, V., Buckley, C. D., Douglas, M., Cody, A. J., Simmons, D. L., & Freeman, S. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11505 · Cited by 186 · see citing works
Kapanadze, T. G., Gamrekelashvili, J., Ma, C., Chan, C., Zhao, F., Hewitt, S. M., Zender, L., Kapoor, V., Felsher, D. W., Manns, M. P., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.06.010 · Cited by 184 · see citing works
Zhou, J., Wu, J., Chen, X., Fortenbery, N. R., Eksioglu, E. A., Kodumudi, K. N., Epling-Burnette, P. K., Dong, J., Djeu, J. Y., & Sheng, W. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.01.007 · Cited by 167 · see citing works
Self-citationGemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug
Rowe, J. M., & Löwenberg, B. (2013) · Blood · doi:10.1182/blood-2013-03-490482 · Cited by 143 · see citing works
Transcription factor networks in B-cell differentiation link development to acute lymphoid leukemia
Somasundaram, R., Prasad, M. A. J., Ungerbäck, J., & Sigvardsson, M. (2015) · Blood · doi:10.1182/blood-2014-12-575688 · Cited by 135 · see citing works
Vasu, S., He, S., Cheney, C., Gopalakrishnan, B., Mani, R., Lozanski, G., Mo, X., Groh, V., Whitman, S. P., Konopitzky, R., et al. (2016) · Blood · doi:10.1182/blood-2015-11-680546 · Cited by 93 · see citing works
Allampallam, K., Shetty, V. T., Mundle, S. D., Dutt, D., Kravitz, H. M., Reddy, P. L., Alvi, S., Galili, N., Saberwal, G. S., Anthwal, S., et al. (2002) · International Journal of Hematology · doi:10.1007/bf02982044 · Cited by 88 · see citing works
Raaijmakers, M. H. G. P. (2012) · International Journal of Hematology · doi:10.1007/s12185-011-1001-x · Cited by 71 · see citing works
S100A8 and S100A9 in inflammatory diseases
Roth, J., Goebeler, M., & Sorg, C. (2001) · The Lancet · doi:10.1016/s0140-6736(05)71610-x · Cited by 66 · see citing works
Stirewalt, D. L., Mhyre, A. J., Marcondes, M., Pogosova‐Agadjanyan, E. L., Abbasi, N., Radich, J. P., & Deeg, H. J. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06923.x · Cited by 52 · see citing works
Chen, X., Bai, F., Sokol, L., Zhou, J., Ren, A., Painter, J. S., Liu, J., Sallman, D. A., Chen, Y. A., Yoder, J. A., et al. (2008) · Blood · doi:10.1182/blood-2008-07-168245 · Cited by 48 · see citing works
Self-citationDisordered Hematopoiesis and Myelodysplasia in the Elderly
Rothstein, G. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.51.3s.3.x · Cited by 48 · see citing works
Innate Immune Signaling in the Myelodysplastic Syndromes
Starczynowski, D. T., & Karsan, A. (2010) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2010.02.008 · Cited by 47 · see citing works
Molecular Pathogenesis of MDS.
Look, A. (2005) · Hematology. American Society of Hematology. Education Program · doi:10.1182/asheducation-2005.1.156 · Cited by 47 · see citing works
Estey, E. H., Koller, C. A., Tsimberidou, A. M., O'Brien, S. M., Beran, M., Cortes, J. E., Tírado-Gómez, M., Lopez‐Berestein, G., & Kantarjian, H. M. (2005) · Blood · doi:10.1182/blood-2004-09-3437 · Cited by 27 · see citing works
Starczynowski, D. T., & Karsan, A. (2010) · Cell Cycle · doi:10.4161/cc.9.5.11156 · Cited by 23 · see citing works
Inflammaging-Associated Metabolic Alterations Foster Development of the MDS Genotype
Wei, S., Eksioglu, E. A., Chen, X., et al. (2015) · Blood · doi:10.1182/blood.v126.23.144.144 · Cited by 7 · see citing works
Self-citationMyelodysplastic syndromes and bone marrow microenvironment
Porta, M. G. D. (2011) · Leukemia Research · doi:10.1016/j.leukres.2011.07.035 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [11]Chen X Eksioglu EA Zhou J Zhang L Djeu J Fortenbery N Induction of myelodysplasia by myeloid-derived suppressor cells The Journal of clinical investigation 2013 11 123 11 4595 4611 24216507 PMC3809779
Cited by
Sorted by citations
Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19
Silvin, A., Chapuis, N., Dunsmore, G., Goubet, A.-G., Dubuisson, A., Derosa, L., Almire, C., Hénon, C., Kosmider, O., Droin, N., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.002 · Cited by 834 · see citing works
The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes
Sallman, D. A., & List, A. (2019) · Blood · doi:10.1182/blood-2018-10-844654 · Cited by 273 · see citing works
Chronic immune response dysregulation in MDS pathogenesis
Barreyro, L., Chlon, T. M., & Starczynowski, D. T. (2018) · Blood · doi:10.1182/blood-2018-03-784116 · Cited by 226 · see citing works
Nutrient Zinc at the Host–Pathogen Interface
Lonergan, Z. R., & Skaar, E. P. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2019.06.010 · Cited by 129 · see citing works
Inflammatory bone marrow microenvironment
Leimkühler, N. B., & Schneider, R. K. (2019) · Hematology · doi:10.1182/hematology.2019000045 · Cited by 82 · see citing works
- Authors
- Eksioglu, E. A., Chen, X., Heider, K.-H., Rueter, B., McGraw, K. L., Basiorka, A. A., Wei, M., Burnette, A., Cheng, P., Lancet, J., Komrokji, R., Djeu, J., List, A., & Wei, S.
- Affiliations
- Moffitt Cancer Center (US)
- Boehringer Ingelheim (Austria) (AT)
- Boehringer Ingelheim (Germany) (DE)
- University of South Florida (US)
- Corresponding author
- Wei, S
- Venue
- Leukemia
- Published
- 2017-01-18
- Volume
- 31
- Issue
- 10
- Pages
- 2172-2180
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC5552472
- OpenAlex
- W2577785715
- Cited by
- 66
- References
- 40
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 4
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (K01CA187020, P30CA076292)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Keywords
- myelodysplastic syndrome, myeloid-derived suppressor cells, CD33, S100A9, hematopoiesis, bone marrow microenvironment, antibody-dependent cellular cytotoxicity, genomic instability, reactive oxygen species, DNA double-strand breaks, immunosuppression, low-risk MDS
- MeSH terms
- Myeloid-Derived Suppressor Cells, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Bone Marrow, Female, Genetic Engineering, Hematopoiesis, Humans, Immunoglobulin Fc Fragments, Male, Middle Aged, Myelodysplastic Syndromes, Signal Transduction, Reactive Oxygen Species, Genomic Instability, Stem Cell Niche, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized, Sialic Acid Binding Ig-like Lectin 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review