ArticleOncotarget2016
Expression and functional characterization of CD33 transcript variants in human acute myeloid leukemia.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics.Frontiers in oncology · 2020Pooled it
- Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.The Journal of clinical investigation · 2024Trial
- CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017Trial
- Overcoming resistance to antibody-drug conjugates: mechanisms and emerging strategies.The oncologist · 2026Review
- Review
- The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.International journal of molecular sciences · 2025Review
- Targeting the membrane-proximal domain of CD33 to maximize the efficacy of natural killer cell-based immunotherapies.Haematologica · 2025Article
- Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2024Article
- Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy.Molecular therapy. Oncology · 2024Article
- First-in-human study of JNJ-67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.Clinical and translational science · 2024Article
- CAR-T Cells Immunotherapies for the Treatment of Acute Myeloid Leukemia-Recent Advances.Cancers · 2023Review
- NK cell defects: implication in acute myeloid leukemia.Frontiers in immunology · 2023Review
- A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges.Frontiers in pharmacology · 2023Review
- Review
- Novel CAR T therapy is a ray of hope in the treatment of seriously ill AML patients.Stem cell research & therapy · 2021Review
- Anti-apoptotic BCL-2 family proteins confer resistance to calicheamicin-based antibody-drug conjugate therapy of acute leukemia.Leukemia & lymphoma · 2020Article
- A novel C2 domain binding CD33xCD3 bispecific antibody with potent T-cell redirection activity against acute myeloid leukemia.Blood advances · 2020Article
- A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes.Frontiers in immunology · 2020Article
- SRSF1 and PTBP1 AreMolecular and cellular biology · 2019Article
- Evaluation of CD33 as a genetic risk factor for Alzheimer's disease.Acta neuropathologica · 2019Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
With the demonstration of improved survival of some acute myeloid leukemia (AML) patients with the CD33 antibody-drug conjugate, gemtuzumab ozogamicin (GO), CD33 has been validated as a target for antigen-specific immunotherapy. Since previous studies identified a CD33 splice variant missing exon 2 (CD33∆E2) and, consequently, the immune-dominant membrane-distal V-set domain, we investigated the expression and functional characteristics of CD33 transcript variants in AML. In primary AML specimens, we not only found full-length CD33 (CD33FL) and CD33∆E2 but also corresponding variants containing an alternate exon 7 predicted to encode a CD33 protein lacking most of the intracellular domain (CD33E7a and, not previously described, CD33∆E2,E7a) in almost all cases. In acute leukemia cell sublines engineered to express individual CD33 splice variants, all splice variants had endocytic properties. CD33FL and CD33E7a mediated similar degrees of GO cytotoxicity, whereas CD33∆E2 and CD33∆E2,E7a could not serve as target for GO. Co-expression of CD33∆E2 did not interfere with CD33FL endocytosis and did not impact CD33FL-mediated GO cytotoxicity. Together, our findings document a greater-than-previously thought complexity of CD33 expression in human AML. They identify CD33 variants that lack exon 2 and are not recognized by current CD33-directed therapeutics as potential target for future unconjugated or conjugated antibodies.
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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.