ArticleHaematologica2010
Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody.
Article in Haematologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 142 citations in OpenAlex.
- Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia.American journal of hematology · 2013Trial
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Clinical evidence and biological mechanisms linking obesity to adverse outcomes in pediatric and adolescent acute lymphoblastic leukemia.Frontiers in oncology · 2026Review
- Unveiling the role of microRNAs, the PI3K/AKT pathway, and their associations in various types of leukemia: a comprehensive review.Blood research · 2025Review
- Intermittent exercise alleviates MI-induced renal injury in mice via IGF-1.Frontiers in physiology · 2025Article
- Advances in the role of the IGF signaling system in myelodysplastic syndromes and acute myeloid leukemia.Frontiers in oncology · 2025Review
- Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges.Current obesity reports · 2024Review
- Insulin-like growth factor 1 receptor inhibits the proliferation of acute myeloid leukaemia cells via NK cell activation.Annals of hematology · 2023Article
- Involvement Value of FLT-3, c-Myc, STAT3, p27, and HOTAIR Gene Expression in Acute Myeloid Leukemia Patients: A Molecular Perspective to a Novel Leukemogenesis Mechanism.International journal of hematology-oncology and stem cell research · 2023Article
- Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia.Life (Basel, Switzerland) · 2022Review
- Article
- Long noncoding RNAs as regulators of pediatric acute myeloid leukemia.Molecular and cellular pediatrics · 2022Review
- Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.International journal of molecular sciences · 2022Review
- The Agglutinin of Common Nettle (Urtica dioica L.) Plant Effects on Gene Expression Related to Apoptosis of Human Acute Myeloid Leukemia Cell Line.Biochemical genetics · 2021Article
- High-throughput proteomic profiling reveals mechanisms of action of AMG925, a dual FLT3-CDK4/6 kinase inhibitor targeting AML and AML stem/progenitor cells.Annals of hematology · 2021Article
- Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter.Children (Basel, Switzerland) · 2021Review
- GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.Cell death & disease · 2021Article
- Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer.Frontiers in pharmacology · 2021Review
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlterations in the PI3K/Akt pathway are found in a wide range of cancers and the development of PI3K inhibitors represents a promising approach to cancer therapy. Constitutive PI3K activation, reflecting an intrinsic oncogenic deregulation of primary blast cells, is detected in 50% of patients with acute myeloid leukemia. However, the mechanisms leading to this activation are currently unknown. As we previously reported IGF-1 autocriny in acute myeloid leukemia cells, we investigated whether IGF-1 signaling was involved in the constitutive activation of PI3K. DESIGN AND
methodsWe analyzed the IGF-1/IGF-1R signaling pathway and PI3K activity in 40 acute myeloid leukemia bone marrow samples. Specific inhibition of IGF-1/IGF-1R signaling was investigated using neutralizing anti-IGF-1R, anti-IGF-1 antibodies or IGF-1 short interfering RNA. The anti-leukemic activity of the neutralizing anti-IGF-1R was tested by analyzing its effects on leukemic progenitor clonogenicity, blast cell proliferation and survival.
resultsIn all samples tested, we found that functional IGF-1R was constantly expressed in leukemic cells. In the acute myeloid leukemia samples with PI3K activation, we found that the IGF-1R was constitutively phosphorylated, although no IGF-1R activating mutation was detected. Specific inhibition of IGF-1R signaling with neutralizing anti-IGF-1R strongly inhibited the constitutive phosphorylation of both IGF-1R and Akt in 70% of the PI3K activated samples. Moreover, both incubation with anti-IGF-1 antibody and IGF-1 short interfering RNA inhibited Akt phosphorylation in leukemic cells. Finally, neutralizing anti-IGF-1R treatment decreased the clonogenicity of leukemic progenitors and the proliferation of PI3K activated acute myeloid leukemia cells.
conclusionsOur current data indicate a critical role for IGF-1 autocriny in constitutive PI3K/Akt activation in primary acute myeloid leukemia cells and provide a strong rationale for targeting IGF-1R as a potential new therapy for this disease.
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