miR-603 promotes cell proliferation and differentiation by targeting TrkB in acute promyelocytic leukemia.

Arsenic trioxide (ATO) treatment effectively prolongs the overall survival of patients with acute promyelocytic leukemia (APL). Mutations in the oncogene PML::RARA were found in patients with ATO-resistant and relapsed APL. However, some relapsed patients do not have such mutations. Here, we performed microarray analysis of samples from newly diagnosed and relapsed APL, and found different microRNA (miRNA) expression patterns between these two groups. Among the differentially expressed miRNAs, miR-603 was expressed at the lowest level in relapsed patients. The expression of miR-603 and its predicted target tropomyosin-related kinase B (TrkB) were determined by PCR and Western blot. Proliferation was measured using an MTT assay, while apoptosis, cell cycle and CD11b expression were analyzed using flow cytometry. In APL patients, the expression of miR-603 was negatively correlated with that of TrkB. miR-603 directly targeted TrkB and downregulated TrkB expression in the APL cell line NB4. miR-603 increased cell proliferation by promoting the differentiation and inhibiting the apoptosis of NB4 cells. This study shows that the miR-603/ TrkB axis may be a potent therapeutic target for relapsed APL.

Predictive value of serum interleukin-6 to determine surgical drainage of deep neck space infection in adults.

PURPOSE: The aim of this study was to determine whether interleukin-6 (IL-6) could be used as a predictor for surgical drainage in deep neck space infection (DNSI). METHODS: A retrospective study was conducted to analyze 69 adult patients newly diagnosed as DNSI from January 2017 to December 2021 at a single center. The patients were treated with either surgical drainage or not. The following clinical data including age, gender, maximum diameter of abscess (MDA), laboratory data, therapeutic modalities, comorbidities, duration of hospitalization and complications were collected and evaluated. RESULTS: Patients in drained group had significantly elevated MDA, IL-6, procalcitonin, C-reactive protein and neutrophil to lymphocyte ratio compared to patients in non-drained group (all P < 0.01). Significant predictors for surgical drainage were IL-6 and MDA as independent factors, with the optimum cutoff values of 52.5 pg/mL and 14.4 mm, respectively. Moreover, the IL-6 had a wider area under the curve than MDA for prediction of surgical drainage in DNSI. CONCLUSIONS: IL-6 as a promising predictor of the need for surgical drainage can be effectively used for routine assessment in the early stage of DNSI to determine the optimal treatments.

Potential role of circular RNA in cyclosporin A-induced cardiotoxicity in rats.

Cyclosporin A (CsA) is a well-known and effective drug that is commonly used in autoimmune diseases and allotransplantation. However, kidney toxicity and cardiotoxicity limit its use. Circular RNAs (circRNAs) play a crucial role in disease, especially cardiovascular disease. We aimed to explore the circRNA expression profiles and potential mechanisms during CsA-induced cardiotoxicity. Sixty male adult Wistar rats were randomly divided into two groups. The CsA group was injected with CsA (15 mg/kg/day body weight) intraperitoneally (ip) for 2 weeks, whereas the control group was injected ip with the same volume of olive oil. We assessed CsA-induced cardiotoxicity by light microscopy, transferase-mediated dUTP nick-end labeling (TUNEL) staining, and electron microscopy. Microarray analysis was used to detect the expression profiles of circRNAs deregulated in the heart during CsA-induced cardiotoxicity. We confirmed the changes in circRNAs by quantitative PCR. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the microarray data were performed. A conventional dose of CsA induced cardiotoxicity in rats. We identified 67 upregulated and 37 downregulated circRNAs compared with those in the control group. Six of 12 circRNAs were successfully verified by quantitative real-time polymerase chain reaction (qRT-PCR). GO analyses of the differentially expressed circRNAs indicated that these molecules might play important roles in CsA-induced cardiotoxicity. KEGG pathway analyses showed that the differentially expressed circRNAs in CsA-induced cardiotoxicity may be related to autophagy or the Hippo signaling pathway. We identified differential circRNA expression patterns and provided more insight into the mechanism of CsA-induced cardiotoxicity. CircRNAs may serve as potential biomarkers or therapeutic targets of CsA-mediated cardiotoxicity in the future.

Evaluation of narrow band imaging for diagnosis of unilateral nasal lesions.

OBJECTIVES: This study aimed to investigate the effect of narrow band imaging (NBI) examination on differentiating diagnosis between benign and malignant neoplasms involving nasal cavity. DESIGN, SETTING, PARTICIPANTS: A retrospective study was conducted to analyse cases from January 2018 to December 2019 at a single centre. A total of 188 consecutive patients who were newly diagnosed with lesions in unilateral nasal cavity underwent complete examination with white light endoscopy (WLE) and NBI endoscopy. Biopsy specimens were harvested from the target lesions and sent to the pathologist for definite diagnosis. Participants with a history of congenital malformation, trauma and surgery in nasal cavity were excluded from the study. MAIN OUTCOME MEASURES: Endoscopic diagnosis was assessed using sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV, respectively). RESULTS: In identifying benign and malignant lesions of nasal cavity, NBI had a significant higher sensitivity (92.7% vs 70.7%, P = .020) and NPV (98% vs 92.3%, P = .032) than WLE, but there were no significant differences between NBI and WLE in specificity (98.6% vs 97.3%, P = .684), accuracy (97.3% vs 91.5%, P = .416) and PPV (95% vs 87.9%, P = .400). CONCLUSION: NBI as an emerging technique can improve the diagnostic accuracy by distinguishing benign and malignant lesions in nasal cavity and remains a promising and helpful adjunct to the endoscopy techniques.

Factors affecting thrombohemorrhagic early death in patients with acute promyelocytic leukemia treated with arsenic trioxide alone.

Acute promyelocytic leukemia (APL) is often accompanied by a potentially devastating coagulopathy. Predictors of thrombohemorrhagic early death (TH-ED)/early bleeding death are not well characterized. In this retrospective study, eleven baseline clinical variables that can be assessed easily and promptly were chosen for evaluation in a cohort of 364 patients with APL who were administered arsenic trioxide (ATO) alone as remission induction therapy. TH-ED was defined as death from bleeding or thrombosis within 30 days after hospital admission. Cox proportional hazards regression model was used for both the univariate and multivariate analyses. Totally, 53 patients died from severe bleeding (51 cases) or thrombosis (2 cases), and at 30 days the cumulative incidences of TH-ED were 14.6%. Six independent risk factors for TH-ED were identified, including relapse, male, white blood cell (WBC) count above 10 × 109/L, fibrinogen level below 1 g/L, D-dimer level above 4 mg/L and increased creatinine level. Increased creatinine level was the most powerful risk factor, followed by WBC count > 10 × 109/L. This study identified risk factors for TH-ED in a large cohort of patients with APL, which enriched clinical information on identifying patients at high risk of TH-ED.

Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia.

Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 109/L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 109/L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

Global research on sinonasal inverted papilloma over the past two decades: a bibliometric analysis.

Objective: This study aimed to investigate the global research status, hot topics, and prospects in the field of sinonasal inverted papilloma (SNIP) through bibliometric analysis. Methods: The literature on SNIP was retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. The bibliometric and visualisation networks of SNIP were constructed using VOSviewer 1.6.18, CiteSpace 6.1. R2, and a bibliometric online analysis platform. Results: A total of 560 original articles about SNIP research were included, involving 2,457 authors from 610 institutions in 45 countries. The number of SNIP publications showed an overall rising trend, with an average annual output of 28 articles and almost 3 times as many articles published in 2020 as in 2002. The analysis of keyword burst detection indicated that EGFR mutation, malignant transformation and infection are emerging research hotspots. Moreover, EGFR mutation, KRAS mutation, malignant tumour, metallothionein 2a gene, pre-operative diagnosis, HPV-negative tumour, and expression were among the 11 key clusters of co-cited references. Conclusions: This study provided a comprehensive, systematic, and objective analysis and visualised knowledge map of SNIP over the past 2 decades. In particular, current hotspots and prospective trends in the field of SNIP have been identified. These results highlight the future direction of SNIP research for rhinologists.

[Prognostic Value of CD56 Expression in Newly Diagnosed Multiple Myeloma Patients and Its Related Factors].

OBJECTIVE: To analyze the effect of CD56 expression on the prognosis of newly diagnosed multiple myeloma (MM) patients and explore the relationship between CD56 with clinical characteristics. METHODS: In this retrospective study, the clinical data and laboratory parameters of 175 newly diagnosed MM patients from February 2015 to December 2020 in the Second Hospital of Anhui Medical University were collected. The patients were divided into CD56+ and CD56- groups based on the expression of CD56, and the general data and laboratory parameters of the two groups were compared. The patients were followed up to June 30, 2021, and progression-free survival (PFS) and overall survival (OS) were recorded. PFS and OS curves of the two groups were plotted respectively, and the survival differences were compared. Univariate and multivariate Cox regression analyses were performed to analyze the effect of CD56 on the prognosis of newly diagnosed MM patients. RESULTS: In 175 newly diagnosed MM patients, 57(32.6%) cases were in the CD56-group and 118 (67.4%) cases in the CD56+ group. There was significant correlation between CD56 expression and ISS stage, ECOG score, platelets, ß2-microglobulin, creatinine, and extramedullary disease (all P <0.05). The incidence of extramedullary disease in the CD56- group was significantly higher than that in the CD56+ group (29.8% vs 12.7%, P =0.006). The median follow-up time of the whole cohort was 23.6 (1.0-78.6) months. The median PFS of patients in CD56+ group and CD56- group were 18.6 (1.2-77.6) and 12.2 (1.0-49.0) months, respectively, and the median OS of the two groups were 27.6 (1.4-77.7) and 19.7 (1.0-78.6) months, respectively. The 2-year PFS rate in the CD56+ group was significantly higher than that in the CD56- group (57.6% vs 36.8%, P =0.010), and the 2-year OS rate in the CD56+ group was higher than that in the CD56- group, but it didn't reach statistical significance (74.6% vs 64.9%, P =0.158). The results of univariate Cox regression analysis showed that the PFS was significantly shorter in newly diagnosed MM patients with advanced age, type IgG, high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05), the OS was significantly shorter in patients with high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05). The results of multivariate Cox regression analysis showed that advanced age, type IgG, elevated lactate dehydrogenase level, extramedullary disease, and CD56- were independent prognostic factors for poor PFS (all P <0.05); and decreased platelet count, elevated lactate dehydrogenase level, and extramedullary disease were independent adverse prognostic factors for OS (all P <0.05), while there was no significant independent correlation between CD56 and OS (P >0.05). CONCLUSION: Most of the newly diagnosed MM patients have positive expression of CD56. Loss of CD56 expression was associated with unfavorable biological and clinical parameters and poor prognosis, suggesting that CD56 has important clinical value in the prognosis of newly diagnosed MM patients.

Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia.

The aim of this study was to determine the efficacy and safety of treatment of pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide (ATO). A total of 19 children (< or = 15 years of age) with newly diagnosed APL were treated with single-agent ATO for remission induction and postremission therapy. Seventeen of the children (89.5%) achieved complete hematologic remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities were minimal and transient. Postremission ATO therapy continued for 3 years; the most common side effect was ATO-induced neutropenia. With a median follow-up of 53 months (range, 23-76 months), the calculated 5-year overall survival and event-free survival were 83.9% and 72.7%, respectively, which are comparable with results achieved by the use of ATRA plus chemotherapy, which is the standard therapy for APL. No chronic arsenic toxicity or second malignancies were found during the follow-up period, and arsenic retention was not significant in patients off treatment more than 24 months. ATO resistance was observed in only 1 patient with a complex karyotype. The results indicate the high efficacy and safety of single-agent ATO regimens in the treatment of children with de novo APL.

[Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells].

OBJECTIVE: To explore the effect of arsenic trioxide (ATO) and daunorubicin (DNR) on phosphatidylserine (PS) exposure and related procoagulant activity of acute promyelocytic leukemia (APL) cells. METHODS: Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 µmol/L ATO and 1 µmol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Lactadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients. RESULTS: ATO induced a decrease of PS exposure on APL cells by flow cytometry and no staining with lactadherin was observed under confocal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was (180 ± 25) s and (220 ± 41) s before and after treatment with ATO, respectively (P < 0.05). The formation of coagulation factors decreased after treatment with ATO (P < 0.05). While coagulation time was (180 ± 25) s and (80 ± 20) s before and after treatment with DNR, respectively (P < 0.05). The formation of coagulation factors increased after treatment with DNR (all P < 0.05). Lactadherin inhibited the procoagulant activities of DNR-treated APL cells (all P < 0.05). CONCLUSIONS: Procoagulant activity is positively correlated with the exposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively.

miR-139-5p Regulates the Proliferation of Acute Promyelocytic Leukemia Cells by Targeting MNT.

Acute promyelocytic leukemia (APL) patients with progressive leukocytosis are more likely to have various complications and poor outcomes. However, the regulatory roles of microRNAs in the leukocytosis of APL have not been clarified. Our study aims to evaluate the effects of miRNAs on leukocytosis during induction therapy of APL patients and explore its potential mechanisms. During induction treatment, patients with white blood cell count higher than 10 × 109/L were divided into leukocytosis group and others were nonleukocytosis group. Using microarray assays, we found that miR-139-5p was significantly downregulated in the leukocytosis group. Elevated expression of miR-139-5p inhibited the proliferation of NB4 cells by arresting the cell cycle and inducing apoptosis. We further identified that MNT was a target of miR-139-5p. miR-139-5p significantly inhibited the proliferation, invasion, and migration function of NB4 cells through targeting MNT. Strategies for regulating miR-139-5p or MNT expression might provide new therapeutic approaches for progressive leukocytosis in APL.

MiRNA-506 presents multiple tumor suppressor activities by targeting EZH2 in nasopharyngeal carcinoma.

OBJECTIVE: MiR-506 has been reported to be associated with multiple malignancies, but its roles in nasopharyngeal cancer (NPC) are not fully understood. Our objective is to demonstrate its effects on NPC and the underlying mechanisms. METHODS: Totally fifteen pairs of NPC and adjacent non-tumorous tissues were collected for the detection of miR-506 and enhancer of zeste homolog 2 (EZH2) expression. Dual luciferase reporter assay was employed for verifying the relationship between miR-506 and EZH2. The flow cytometry and MTT assays were employed to explore the effects of miR-506 and EZH2 on the cell apoptosis and proliferation, respectively. Wound closure and transwell assays were used to evaluate the cell migration and invasion abilities. Western blotting or RT-qPCR assays were applied to detect the alterations of miR-506, EZH2 and epithelial-mesenchymal transition (EMT)-related markers. Morphological changes of cells with EMT were assessed by light microscopy. RESULTS: MiR-506 was significantly decreased and EZH2 was obviously increased in NPC tissues. Overexpression of miR-506 decreased the EZH2 level, promoted apoptosis, inhibited proliferation, invasion and migration of NPC cells. Accordingly, miR-506 overexpression attenuated EMT process of NPC cells as demonstrated by the alterations of EMT-related markers and the morphological changes. In addition, the luciferase assay proved that miR-506 directly targeted EZH2. Furthermore, the overexpression of EZH2 reversed the tumor-suppressive effects induced by miR-506 mimics. CONCLUSION: MiR-506 acted as a tumor suppressor to promote apoptosis and inhibit invasion and migration via directly targeting EZH2. MiR-506 can be a candidate target for gene therapy against NPC.

Comparative analysis of causes and predictors of early death in elderly and young patients with acute promyelocytic leukemia treated with arsenic trioxide.

PURPOSE: Early death (ED) is the main cause of acute promyelocytic leukemia (APL) treatment failure, and the ED rate is higher for elderly patients than that for young ones. To date, no studies have been found focusing on ED in elderly patients with APL. METHODS: This study retrospectively analyzed the clinical data of 409 consecutive patients with APL (139 patients ≥ 50 years old, 270 patients < 50 years old). All patients received arsenic trioxide alone as induction therapy. The baseline clinical characteristics and ED occurrence and predictors between elderly and young patients with APL were compared and analyzed. RESULTS: The clinical features of elderly patients at admission were not significantly different from those of young ones. The ED rate of elderly patients was significantly greater than that of young patients (23.74% vs 11.85%, P = 0.0018). Hemorrhage is the main cause of ED in elderly patients, followed by infection and differentiation syndrome. From the 15th to 30th days of treatment, elderly patients had a higher mortality rate than that of young patients (7.83% vs 2.06%, P = 0.009). Male, white blood cell (WBC) count > 10 × 109/L, fibrinogen < 1.0 g/L and low albumin levels were independent risk factors for ED in elderly patients, while ED was only correlated with WBC count, fibrinogen and creatinine levels in young patients. CONCLUSION: The results of this study may help design more rational treatment plans for elderly patients with APL based on early mortality risk to reduce the ED rate.

Procoagulant activity and phosphatidylserine of amniotic fluid cells.

Amniotic fluid (AF) may induce disseminated intravascular coagulation (DIC) when it enters maternal circulation by breaching the placental-maternal circulation barrier. The precise mechanism of the procoagulant activity of AF is unclear, but tissue factor (TF) has been proposed to be the main cause. As one constituent of AF, AF cells accumulate and undergo apoptosis continuously. Therefore, we speculate that AF cells have procoagulant activity due to the externalisation of phosphatidylserine (PS). The present study aims to demonstrate that, in addition to TF, the PS that is externalised on AF cells is important for the procoagulant activity of AF. Ten AF samples from parturient women were analysed using lactadherin as the probe for PS. Anti-TF antibody also was used to identify TF and its associated coagulation functions in AF cells. Normal platelets, neutrophils, and lymphocytes were harvested as controls. Confocal microscopy and flow cytometry was used to assess PS expression on AF cells. The procoagulant activity of AF cells was demonstrated by a plasma coagulation assay and further confirmed by factor Xase/prothrombinase assays. PS and TF were present on most AF cells, providing substantial procoagulant activity. Furthermore, factor Xase and prothrombinase assays showed that AF cells substantially enforced the activation of factor X and prothrombin. PS on AF cells is an important procoagulant source for AF. Lactadherin is an ideal anticoagulant for inhibiting the procoagulant activity of AF cells.

Role of miRNA-21 in the diagnosis and prediction of treatment efficacy of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) has a poor prognosis and requires early diagnosis and treatment. The aim of the present study was to investigate the difference between microRNA-21 (miRNA-21) expression in the plasma and cerebrospinal fluid (CSF) of patients with PCNSL, and to discuss the importance of miRNA-21 in its diagnostic and therapeutic evaluation. The research subjects were confirmed as patients with PCNSL with histopathological lesions at The First Affiliated Hospital of Harbin Medical University (Harbin, China) between December 2011 and 2017. Comparisons were drawn between the PCNSL, glioblastoma and the healthy control groups. CSF and plasma specimens were obtained from patients with PCNSL prior to chemotherapy, and CSF specimens were also obtained following chemotherapy. Plasma specimens were taken from patients with glioblastoma and the healthy control group. Using reverse transcription-quantitative polymerase chain reaction analysis, it was revealed that plasma miRNA-21 expression level had a notable diagnostic value in distinguishing PCNSL from glioblastoma, another common neurological tumor. Moreover, miRNA-21 expression levels in the plasma correlated positively with those in the CSF. Therefore, miRNA-21 in the plasma may be used as a novel diagnostic biomarker to distinguish patients with PCNSL from those with glioblastoma, whereas miRNA-21 in the CSF may have potential as a predictor of chemotherapeutic effect in PCNSL.

Increased procoagulant activity of red blood cells in the presence of cisplatin.

BACKGROUND: Cisplatin based chemotherapy is a well recognized risk factor for coagulation disorders and thrombosis. The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood. METHODS: Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n = 10) and healthy adults (n = 6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry. RESULTS: Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9 +/- 0.5)% on control RBCs to (68.0 +/- 3.5)% on RBCs treated with 10 micromol/L cisplatin for 24 hours. CONCLUSIONS: Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.

Characteristics of fibrinolytic disorders in acute promyelocytic leukemia.

OBJECTIVES: Catastrophic hemorrhage remains the main cause of acute promyelocytic leukemia (APL) treatment failure. This study was aimed to study the pathogenesis of coagulopathy in patients with APL. METHODS: Multiple procoagulant and profibrinolytic parameters in plasma and peripheral leukocytes from 24 patients with newly diagnosed APL accompanied by coagulopathy before and after arsenic trioxide (ATO) treatment were evaluated. RESULTS: Prior to the treatment, the patients had elevated D-dimer and decreased fibrinogen levels. Plasma urokinase-type plasminogen activator receptor (uPAR) and plasmin-ɑ2 antiplasmin complexes (PAP) levels, plasmin (Pn) activity, and cell surface levels of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) were significantly higher; plasma plasminogen activator inhibitor-1 (PAI-1) levels and plasminogen (Pg) activity were significantly decreased; plasma plasminogen activator (PA) activity, uPA and tPA levels; and cell surface levels of uPAR and annexin II were not significantly different from levels in the control group. During ATO treatment, both patients' plasma PA activity and uPAR on leukocytes gradually increased, annexin II on leukocytes increased initially and decreased afterwards, and tPA and uPA on leukocytes remained consistently higher in the patients than in the controls. Other parameters gradually tended toward normal values. CONCLUSIONS: In APL, activated coagulation system activated fibrinolytic system, and increased uPAR levels could contribute to the hyperfibrinolysis. Annexin II might not be involved in the coagulopathy.

Development of a risk grading system to identify patients with acute promyelocytic leukemia at high risk of early death.

BACKGROUND: Early death (ED) rate in acute promyelocytic leukemia (APL) remains high. Some studies have identified prognostic factors capable of predicting ED, whereas no risk rating system for ED has been reported in the literature. In this study, a risk classification system was built to identify subgroup at high risk of ED among patients with APL. METHODS: Totally, 364 consecutive APL patients who received arsenic trioxide as induction therapy were included. Ten baseline clinical characteristics were selected for analysis, and they were de novo/relapse, age, sex, white blood cell count, platelet count, serum fibrinogen, creatinine, uric acid, aspartate aminotransferase, and albumin. Using a training cohort (N=275), a multivariable logistic regression model was constructed, which was internally validated by the bootstrap method and externally validated using an independent cohort (N=89). Based on the model, a risk classification system was designed. Then, all patients were regrouped into de novo (N=285) and relapse (N=79) cohorts and the model and risk classification system were applied to both cohorts. RESULTS: The constructed model included 8 variables without platelet count and sex. The model had excellent discriminatory ability (optimism-corrected area under the receiver operator characteristic curve=0.816±0.028 in the training cohort and area under the receiver operator characteristic curve=0.798 in the independent cohort) and fit well for both the training and independent data sets (Hosmer-Lemeshow test, P=0.718 and 0.25, respectively). The optimism-corrected calibration slope was 0.817±0.12. The risk classification system could identify a subgroup comprising ~25% of patients at high risk of ED in both the training and independent cohorts (OR=0.140, P<0.001 and OR=0.224, P=0.027, respectively). The risk classification system could effectively identify patient subgroups at high risk of ED in not only de novo but also relapse cohorts (OR=0.233, P<0.001 and OR=0.105, P=0.001, respectively). CONCLUSION: All the results highlight the high practical value of the risk classification system.

[Effect of Daunorubicin on Release and Procoagulant Activity of Microparticles Derived from Acute Promyelocytic Leukemia Cells].

OBJECTIVE: To investigate the effect of daunorubicin on the number and procoagulant activity of Microparticles derived from acute promyelocytic leukemia(APL) cells. METHODS: APL cells were isolated from bone Marrow of 5 newly diagnosed APL patients, the bone marrow mononuclear cells were collected from 5 patients with iron deficiency anemia as control.APL cells were treated with different concentration of daunorubicin(0.1,0.5,1.0 and 2.0µmol/L) for 24 h. Microparticles were extracted from the cell culture medium for qualitative anaysis of the extracted microparticles.The morphologic features of the microparticles were observed by transmission electron microscopy.The number of microparticles was detected by flow cytometry.The procoagulant activity of microparticles was measured by recalcification time assays. RESULTS: Under a transmission electron microscope, theextracted microparticles took a round or oval morphology with a transparent center,and their diameters were arund 100nm, consistent with the morphological characteristics of microparticles. Compared with bone marrow mononuclear cells-derived microparticles,the counts of the bone marrow APL cells-derived microparticles significantly increased(P<0.05).Daunorubicin increased the shedding of microparticles in a dose-dependent manner(r=0.73,P<0.01).Compared with normal bone marrow mononuclear cells-derived microparticles,bone marrow APL cells-derived microparticles showed higher procoagulant activity(P<0.05).Daunorubicin treatment enhanced the prccoagulant activity of APL cells-derived microparticles which paralleled the increasing drug concentrations(r=-0.78,P<0.01). CONCLUSION: Daunorubicin can promote the release of APL cells-derived microparticles and enhance their related procoagulan activity.