ArticleBritish journal of haematology2014
SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia.
Article in British journal of haematology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Approval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm.Blood advances · 2020Trial
- CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia.Haematologica · 2019Trial
- Review
- B-Lymphoid Blast Phase-Chronic Myeloid Leukemia: Current Therapeutics.International journal of molecular sciences · 2022Review
- New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy.International journal of molecular sciences · 2022Review
- Relapse of tagraxofusp treated blastic plasmacytoid dendritic cell neoplasm with loss of CD123 expression.Journal of hematopathology · 2022Article
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies.Cancers · 2020Review
- Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.Frontiers in immunology · 2020Review
- Review
- Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML.International journal of molecular sciences · 2019Review
- DNA methylation profiling reveals a pathological signature that contributes to transcriptional defects of CD34Molecular oncology · 2018Article
- Role of the β Common (βc) Family of Cytokines in Health and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- Targeting Leukemia Stem Cells in the Bone Marrow Niche.Biomedicines · 2018Review
- A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.Nature communications · 2018Article
- Article
- Overcoming the Immunosuppressive Tumor Microenvironment of Hodgkin Lymphoma Using Chimeric Antigen Receptor T Cells.Cancer discovery · 2017Article
- Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors.Hematology/oncology clinics of North America · 2017Review
- High CD123 levels enhance proliferation in response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression.Blood advances · 2017Article
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL-401 and SL-501 decreased the absolute numbers of viable CD34(+) /CD38(-) /CD123(+) CML progenitor cells by inducing apoptosis. IL3-targeting agents reduced clonogenic growth and diminished the fraction of primitive long-term culture-initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI-resistant CML blast crisis. These data suggest that the DT-IL3 fusion proteins, SL-401 and SL-501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.