ArticleCancer medicine2024
Multi-Omic Analysis Reveals the Impact of Bortezomib in Hyperleukocytic Acute Myeloid Leukemia.
Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHyperleukocytic acute myeloid leukemia (HL-AML) is associated with early complications and high mortality rates, highlighting the urgent need for more effective therapeutic strategies.
methodsThis study conducted label-free proteomic analysis on serum from HL-AML and non-HL AML (NHL-AML) patients, integrating the data with the OHSU transcriptomic database. Flow cytometry was used to evaluate the in vitro impact of bortezomib. The in vivo effectiveness of bortezomib was assessed using the patient-derived xenograft (PDX) model of HL-AML.
resultsThrough integrated analysis of serum proteomics and transcriptomics, we observed an abnormal enrichment of the NF-kappa B pathway in HL-AML, suggesting its potential as a novel therapeutic target. Given that bortezomib is an inhibitor of the NF-kappa B pathway, HL-AML bone marrow cells were treated with varying concentrations of bortezomib (0, 5, 10, and 20 nM) in vitro. The results indicated a significant cytotoxic effect of bortezomib on HL-AML cells, accompanied by increased apoptosis rates and decreased proliferation. Co-administration of bortezomib with the frontline clinical chemotherapeutic regimen of daunorubicin and cytarabine (DA regimen) significantly extended mouse survival. Bone marrow immunophenotyping showed reductions in CD45
conclusionsThese data suggest that combination therapy involving bortezomib and the DA regimen may represent a promising strategy for HL-AML.
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