ArticleLeukemia2006
Cytotoxic activity of gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukemia correlates with the expression of protein kinase Syk.
Article in Leukemia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 47 citations in OpenAlex.
- Trial
- Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study.Haematologica · 2014Trial
- Trial
- Trial
- Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.Journal of translational medicine · 2024Article
- Emerging immuno-oncology targets in Myelodysplastic Syndromes (MDS).Current problems in cancer · 2022Review
- Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy.Frontiers in immunology · 2022Review
- Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia.Frontiers in oncology · 2021Review
- Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure.Biology · 2020Article
- Epigenetic polypharmacology: A new frontier for epi-drug discovery.Medicinal research reviews · 2020Review
- Overexpression of annexin A5 might guide the gemtuzumab ozogamicin treatment choice in patients with pediatric acute myeloid leukemia.Therapeutic advances in medical oncology · 2020Article
- Syk interacts with and phosphorylates nucleolin to stabilize Bcl-x(L) mRNA and promote cell survival.Molecular and cellular biology · 2014Article
- Article
- Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin.Frontiers in bioscience (Landmark edition) · 2013Review
- A peptide-based biosensor assay to detect intracellular Syk kinase activation and inhibition.Biochemistry · 2012Article
- Article
- Therapy with azanucleosides for myelodysplastic syndromes.Nature reviews. Clinical oncology · 2010Review
- Article
- Proteomic and genetic approaches identify Syk as an AML target.Cancer cell · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) cells express the cell surface antigen CD33 that, upon ligation with a monoclonal antibody (mAb), is a downregulator of cell growth in a Syk-dependent manner. An anti-CD33 mAb coupled to a toxin, gemtuzumab ozogamicin (GO), is used for the treatment of AML (Mylotarg). Therefore, we investigated whether the response of AML cells to GO treatment also depends on Syk expression. Forty primary AML samples (25 Syk-positive and 15 Syk-negative) were tested for their response to the anti-proliferative effects of GO and unmodified anti-CD33 mAb. A correlation between Syk expression and the response of leukemia cells to GO and anti-CD33 mAb was found. 'Blocking' of Syk by small interfering RNA resulted in unresponsiveness of AML cells to both GO and anti-CD33 mAb-mediated cytotoxicity. Syk upregulation by the de-methylating agent 5-azacytidine (5-aza) induced re-expression of Syk in some cases, resulting in enhanced GO and anti-CD33-mediated inhibition of leukemia cell growth. Thus, the cytotoxicity of both GO and anti-CD33 in primary AML samples was associated with Syk expression. 5-Aza restored Syk and increased the sensitivity of originally Syk-negative, non-responsive cells to CD33 ligation to levels of Syk-positive cells. These data have clinical significance for predicting response to GO and designing clinical trials.
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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.