The efficacy of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL) is widely accepted. It is necessary to determine the concentration of arsenic due to its toxicity. The profiles of arsenic speciation in patients with relapsed or refractory APL have been demonstrated in few reports. Arsenic metabolite concentrations in the plasma of patients with newly diagnosed APL during the first course of arsenic remission induction therapy were determined, and the complicated change pattern of these metabolite concentrations in this phase is described for the first time in this study. We demonstrated that the concentration of trivalent inorganic arsenic (As(III)), which is regarded as the most effective and toxic, was much lower than those of other metabolites. Concentrations of the same arsenic metabolites were obviously distinct among various individuals. We infer that determination of the metabolites separately is necessary, and cannot be replaced by total arsenic determination. In addition, the amount of methylated metabolites of arsenic increased during the first course of ATO therapy, and these metabolites might therefore play an increasingly important role. Further research should be carried out to study the relationship between arsenic metabolite concentrations and efficacy, as well as side effects in patients with APL treated with ATO.
BackgroundStem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear.MethodsThe present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods.ResultsWe found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML.ConclusionOverall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies.
Arsenic trioxide (ATO)-induced hepatotoxicity is often observed in acute promyelocytic leukemia (APL) patients and decreases therapeutic effect of ATO. Thus, concerns over hepatotoxicity have been raised. The aim of this study was to explore some noninvasive clinical indicators that can be used to guide the individualized application of ATO in the future. APL patients treated with ATO were identified retrospectively via electronic health records at our hospital from August 2014 through August 2019. APL patients without hepatotoxicity were selected as controls. The association between putative risk factors and ATO-induced hepatotoxicity was estimated with ORs and 95% CIs, which were calculated using the chi-square test. The subsequent multivariate analysis was performed using logistic regression analysis. In total, 58.04% of patients experienced ATO-induced hepatotoxicity during the first week. Elevated hemoglobin (OR 8.653, 95% CI, 1.339–55.921), administration of nonprophylactic hepatoprotective agents (OR 36.455, 95% CI, 7.409–179.364), non-single-agent ATO to combat leukocytosis (OR 20.108, 95% CI, 1.357–297.893) and decreased fibrinogen (OR 3.496, 95% CI, 1.127–10.846) were found to be statistically significant risk factors for ATO-induced hepatotoxicity. The area under the ROC curve values were 0.846 for “overall ATO-induced hepatotoxicity” and 0.819 for “early ATO-induced hepatotoxicity.” The results revealed that hemoglobin ≥ 80 g/L, nonprophylactic hepatoprotective agents, and non-single-agent ATO and fibrinogen < 1 g/L are risk factors for ATO-induced hepatotoxicity in newly diagnosed APL patients. These findings can enhance the clinical diagnosis of hepatotoxicity. Prospective studies should be performed in the future to validate these findings.
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