[Predictive Value of Acute Phase Proteins on the Prognosis of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To analyze the predictive value of acute phase proteins (APPs) on the prognosis of patients with acute myeloid leukemia (AML). METHODS: 293 AML patients who met the study requirements from January 2015 to April 2021 were collected, their clinical characteristics and pre-treatment APPs levels ï¼»including albumin (ALB), fibrinogen (FIB), C-reactive protein (CRP), Ferritin (FER)ï¼½ were followed up and investigated. Pearson correlation coefficient was used to analyze the correlation between APPs. Logistic regression was used to analyze the risk factors for mortality in AML patients. ROC curve was used to analyze the predictive value of APP for mortality in AML patients, and Kaplan-Meier survival analysis was used to compare the effect of APPs on complete remission (CR) rate, overall survival (OS), disease-free survival (DFS), and progression-free survival rate (PFS) of AML patients. RESULTS: Pearson correlation analysis showed that there were negative correlations between ALB and CRP (r=-0.134, P=0002), as well as ALB and FER (r=-0.148, P=0.001). There were correlations between FER and CRP (r=0361, P＜0.001), as well as FER and FIB (r=0.293, P＜0.001). Logistic regression analysis showed that advanced age (>50 years) (OR=1.87, 95% CI=1.25-2.15, P＜0.001), relapse after treatment (OR=2.11, 95% CI=111-3.18, P=0.003), FLT3-ITD mutation (OR=2.59, 95% CI=1.10-4.12, P＜0.001), CRP≥524 mg/L (OR=1.21, 95% CI=1.02-2.14, P=0.024), CFA (CFA=CRP*FIB/ ALB)≥3 (OR=2.41, 95% CI=1.65-6.47, P＜0.001), and FER≥1145.58 mg/ml (OR=1.67, 95% CI=1.15-3.75, P＜0.001) were the risk factors for the survival of AML patients. ROC curve analysis showed that FER (AUC=0.752, 95% CI=0.681-0823, P＜0.001, the best cut-off value=1220.56 mg/ml) and CFA (AUC=0.804, 95% CI=0.741-0.868, P＜0.001, the best cut-off value=3.00) had higher predictive value for the survival of AML patients. The remission rate, PFS, DFS, and OS in the low CFA group (CFA≤3) were significantly higher than those in the high CFA group (CFA＞3), and the overall mortality rate was lower than that in the high CFA group; the remission rate, PFS, DFS, and OS in the low FER group (FER≤1220.56 mg/ml) were significantly higher than those in the high FER group (FER＞1220.56 mg/ml), while the overall mortality rate was lower than that in the high FER group, and the difference is statistically significant. CONCLUSION: The CFA value and FER level before treatment in AML patients can independently predict the prognosis of patients, and high levels of CFA and FER are associated with poor prognosis of AML patients.

Platelet phagocytosis by leukocytes in a patient with cerebral hemorrhage and thrombocytopenia caused by gram-negative bacterial infection.

Bacteria-induced thrombocytopenia is a common clinical disease that is often ignored by clinical and scientific research. Thus, exploring the mechanism and principle of bacteria-induced thrombocytopenia could facilitate the development of new diagnostic, preventative, and treatment modalities for thrombocytopenia. This case report describes a case of platelet phagocytosis by neutrophils and monocytes in a patient with cerebral hemorrhage and thrombocytopenia caused by gram-negative bacterial infection. After the infection was eradicated, platelet phagocytosis was alleviated, and his platelet count normalized. Cellular immunity may be an important cause of bacteria-induced thrombocytopenia in patients with cerebral hemorrhage.

Histone methyltransferase EZH2 epigenetically affects CCNA1 expression in acute myeloid leukemia.

Cyclin A1 (CCNA1) is an alternative A-type cyclin that is expressed in acute myeloid leukemia (AML). However, its functions in AML cell chemoresistance, an important cause for mortality, are incompletely understood. The purpose of this study was to expound the role and potential mechanism of CCNA1 in AML cell chemoresistance. Upregulation of CCNA1 promoted resistance of AML cells to PKC412, AC220, and AraC. Mechanistically, it was confirmed that CCNA1 transcription was negatively regulated by forkhead box A2 (FOXA2), and the downregulation of FOXA2 promoted chemoresistance in AML cells. Moreover, the promoter sequence of CCNA1 has a significant H3K27me3 modification. Enhancer of zeste homolog 2 (EZH2) enhanced H3K27me3 modification of CCNA1 promoter to inhibit CCNA1 expression, thus promoting sensitivity of AML cells to drugs. Taken together, these findings lead to deeper insights into the mechanism of AML cell chemo-sensitivity by inhibiting CCNA1 at the transcriptional level.

Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes.

The islet in type 2 diabetes (T2DM) and the brain in neurodegenerative diseases share progressive cell dysfunction, increased apoptosis, and accumulation of locally expressed amyloidogenic proteins (islet amyloid polypeptide (IAPP) in T2DM). Excessive activation of the Ca(2+)-sensitive protease calpain-2 has been implicated as a mediator of oligomer-induced cell death and dysfunction in neurodegenerative diseases. To establish if human IAPP toxicity is mediated by a comparable mechanism, we overexpressed human IAPP in rat insulinoma cells and freshly isolated human islets. Pancreas was also obtained at autopsy from humans with T2DM and nondiabetic controls. We report that overexpression of human IAPP leads to the formation of toxic oligomers and increases beta cell apoptosis mediated by increased cytosolic Ca(2+) and hyperactivation of calpain-2. Cleavage of alpha-spectrin, a marker of calpain hyperactivation, is increased in beta cells in T2DM. We conclude that overactivation of Ca(2+)-calpain pathways contributes to beta cell dysfunction and apoptosis in T2DM.