-
International Journal of Laboratory... Dec 2023
Recurrent RARG trinary fusion and ligand binding domain truncation in variant acute promyelocytic leukemia resistant to retinoic acid but sensitive to homoharringtonine-based therapy.
Topics: Humans; Leukemia, Promyelocytic, Acute; Tretinoin; Homoharringtonine; Ligands; Protein Domains; Oncogene Proteins, Fusion; Retinoic Acid Receptor alpha
PubMed: 37605819
DOI: 10.1111/ijlh.14150 -
Blood Science (Baltimore, Md.) Apr 2024An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we...
An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529-0.870, = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530-0.938, = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940-0.993, = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927-0.993, = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397-0.863, = .007; CIR: HR: 0.551, 95% CI: 0.353-0.861, = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424-0.896, = .011; CIR: HR: 0.617, 95% CI: 0.388-0.979, = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.
PubMed: 38742239
DOI: 10.1097/BS9.0000000000000189 -
Biomedicine & Pharmacotherapy =... Jul 2024The plant alkaloid homoharringtonine (HHT) is a Food and Drug Administration (FDA)-approved drug for the treatment of hematologic malignancies. In addition to its...
(Homo-)harringtonine prevents endothelial inflammation through IRF-1 dependent downregulation of VCAM1 mRNA expression and inhibition of cell adhesion molecule protein biosynthesis.
The plant alkaloid homoharringtonine (HHT) is a Food and Drug Administration (FDA)-approved drug for the treatment of hematologic malignancies. In addition to its well-established antitumor activity, accumulating evidence attributes anti-inflammatory effects to HHT, which have mainly been studied in leukocytes to date. However, a potential influence of HHT on inflammatory activation processes in endothelial cells, which are a key feature of inflammation and a prerequisite for the leukocyte-endothelial cell interaction and leukocyte extravasation, remains poorly understood. In this study, the anti-inflammatory potential of HHT and its derivative harringtonine (HT) on the TNF-induced leukocyte-endothelial cell interaction was assessed, and the underlying mechanistic basis of these effects was elucidated. HHT affected inflammation in vivo in a murine peritonitis model by reducing leukocyte infiltration and proinflammatory cytokine expression as well as ameliorating abdominal pain behavior. In vitro, HT and HHT impaired the leukocyte-endothelial cell interaction by decreasing the expression of the endothelial cell adhesion molecules intracellular adhesion molecule -1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was mediated by a bipartite mechanism. While HHT did not affect the prominent TNF-induced pro-inflammatory NF-ĸB signaling cascade, the compound downregulated the VCAM1 mRNA expression in an IRF-1-dependent manner and diminished active ICAM1 mRNA translation as determined by polysome profiling. This study highlights HHT as an anti-inflammatory compound that efficiently hampers the leukocyte-endothelial cell interaction by targeting endothelial activation processes.
Topics: Animals; Down-Regulation; Vascular Cell Adhesion Molecule-1; Inflammation; RNA, Messenger; Humans; Interferon Regulatory Factor-1; Mice; Homoharringtonine; Male; Human Umbilical Vein Endothelial Cells; Anti-Inflammatory Agents; Intercellular Adhesion Molecule-1; Endothelial Cells; Mice, Inbred C57BL; Cell Adhesion Molecules; Leukocytes
PubMed: 38865849
DOI: 10.1016/j.biopha.2024.116907 -
Panminerva Medica Feb 2024
PubMed: 38411405
DOI: 10.23736/S0031-0808.24.05064-X