ArticleLeukemia2000
Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias.
Article in Leukemia, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02661022 (A Phase 1/2 Open Label Study of SL-401 in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma), which is not on this map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase 1/2 Open Label Study of SL-401 in Combination With Pomalidomide and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Approval of tagraxofusp-erzs for blastic plasmacytoid dendritic cell neoplasm.Blood advances · 2020Trial
- Cellular immunotherapy for acute myeloid leukemia: from bench to bedside.Immunotherapy advances · 2026Review
- Discovery and investigation of the truncation of the (GGGGS)n linker and its effect on the productivity of bispecific antibodies expressed in mammalian cells.Bioprocess and biosystems engineering · 2025Article
- Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm.Haematologica · 2024Review
- CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm.International journal of molecular sciences · 2023Review
- CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Cell-based and antibody-mediated immunotherapies directed against leukemic stem cells in acute myeloid leukemia: Perspectives and open issues.Stem cells translational medicine · 2020Review
- CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies.Cancers · 2020Review
- Treatment of Acute Myeloid Leukemia in the Era of Genomics-Achievements and Persisting Challenges.Frontiers in genetics · 2020Review
- Updates in Novel Therapies for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN).Current hematologic malignancy reports · 2019Review
- Review
- Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML.International journal of molecular sciences · 2019Review
- Clinical Activity and Tolerability of SL-401 (Tagraxofusp): Recombinant Diphtheria Toxin and Interleukin-3 in Hematologic Malignancies.Biomedicines · 2019Review
- Targeted Diphtheria Toxin-Based Therapy: A Review Article.Frontiers in microbiology · 2019Review
- Recent developments in the treatment of blastic plasmacytoid dendritic cell neoplasm.Therapeutic advances in hematology · 2019Review
- A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells.Blood advances · 2018Article
- Novel antibody-cytokine fusion proteins featuring granulocyte-colony stimulating factor, interleukin-3 and interleukin-4 as payloads.Journal of biotechnology · 2018Article
- [The study of expression and prognostic value of CD123 in acute myeloid leukemia bone marrow blasts].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017Article
- Optimization of the Expression of DT386-BR2 Fusion Protein inAdvanced biomedical research · 2017Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Leukemic blasts from patients with acute phase chronic myeloid leukemic and refractory acute myeloid leukemia are highly resistant to a number of cytotoxic drugs. To overcome multi-drug resistance, we engineered a diphtheria fusion protein by fusing human interleukin-3 (IL3) to a truncated form of diphtheria toxin (DT) with a (G4S)2 linker (L), expressed and purified the recombinant protein, and tested the cytotoxicity of the DTLIL3 molecule on human leukemias and normal progenitors. The DTLIL3 construct was more cytotoxic to interleukin-3 receptor (IL3R) bearing human myeloid leukemia cell lines than receptor-negative cell lines based on assays of cytotoxicity using thymidine incorporation, growth in semi-solid medium and induction of apoptosis. Exposure of mononuclear cells to 680 pM DTLIL3 for 48 h in culture reduced the number of cells capable of forming colonies in semi-solid medium (colony-forming units leukemia) > or =10-fold in 4/11 (36%) patients with myeloid acute phase chronic myeloid leukemia (CML) and 3/9 (33%) patients with acute myeloid leukemia (AML). Normal myeloid progenitors (colony-forming unit granulocyte-macrophage) from five different donors treated and assayed under identical conditions showed intermediate sensitivity with three- to five-fold reductions in colonies. The sensitivity to DTLIL3 of leukemic progenitors from a number of acute phase CML patients suggests that this agent could have therapeutic potential for some patients with this disease.
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What OpenQuestion holds
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.