ArticleLeukemia2013
Src kinase-induced phosphorylation of annexin A2 mediates glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia.
Article in Leukemia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- ANXA1 overexpression promotes B cell acute lymphoblastic leukemia progression and resistance by regulating fatty acid metabolism through PI3K/Akt signaling.Molecular and cellular biochemistry · 2026Article
- ANXA2 in cancer: aberrant regulation of tumour cell apoptosis and its immune interactions.Cell death discovery · 2025Review
- Fusion-specific chromatin profiles mediate transcriptional heterogeneity in MLL-rearranged acute lymphoblastic leukemia.Blood advances · 2025Article
- Article
- Review
- PIN1 promotes the metastasis of cholangiocarcinoma cells by RACK1-mediated phosphorylation of ANXA2.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation.Cellular and molecular life sciences : CMLS · 2023Article
- Role of Fyn in hematological malignancies.Journal of cancer research and clinical oncology · 2023Review
- Açaí (Metabolites · 2023Article
- Review
- GNAQ T96S mutation abrogates the ability of wild-type GNAQ to induce apoptosis by phosphorylating annexin A2 in natural killer/T cell lymphoma.Cancer science · 2022Article
- MLL-Rearranged Acute Lymphoblastic Leukemia.Current hematologic malignancy reports · 2020Review
- Integrated bioinformatics analysis of the crucial candidate genes and pathways associated with glucocorticoid resistance in acute lymphoblastic leukemia.Cancer medicine · 2020Article
- Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia.Nature cancer · 2020Article
- S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer.Frontiers in cell and developmental biology · 2020Article
- Crucial role of Anxa2 in cancer progression: highlights on its novel regulatory mechanism.Cancer biology & medicine · 2019Article
- Distinct prognostic values of Annexin family members expression in acute myeloid leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Article
- Differential network analysis and protein-protein interaction study reveals active protein modules in glucocorticoid resistance for infant acute lymphoblastic leukemia.Molecular medicine (Cambridge, Mass.) · 2019Article
- Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells.Breast cancer research : BCR · 2019Article
- Emerging targets in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MLL-rearranged infant acute lymphoblastic leukemia (ALL) (<1 year of age) are frequently resistant to glucocorticoids, like prednisone and dexamethasone. As poor glucocorticoid responses are strongly associated with therapy failure, overcoming glucocorticoid resistance may be a crucial step towards improving prognosis. Unfortunately, the mechanisms underlying glucocorticoid resistance in MLL-rearranged ALL largely remain obscure. We here defined a gene signature that accurately discriminates between prednisolone-resistant and prednisolone-sensitive MLL-rearranged infant ALL patient samples, demonstrating that, among other genes, high-level ANXA2 is associated with prednisolone resistance in this type of leukemia. Further investigation demonstrated that the underlying factor of this association was the presence of Src kinase-induced phosphorylation (activation) of annexin A2, a process requiring the adapter protein p11 (encoded by human S100A10). shRNA-mediated knockdown of either ANXA2, FYN, LCK or S100A10, all led to inhibition of annexin A2 phosphorylation and resulted in marked sensitization to prednisolone. Likewise, exposure of prednisolone-resistant MLL-rearranged ALL cells to different Src kinase inhibitors exerting high specificity towards FYN and/or LCK had similar effects. In conclusion, we here present a novel mechanism of prednisolone resistance in MLL-rearranged leukemias, and propose that inhibition of annexin A2 phosphorylation embodies a therapeutic strategy for overcoming resistance to glucocorticoids in this highly aggressive type of leukemia.
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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.