Mitochondrial quality control includes mechanisms such as mitochondria-derived vesicles, fusion / fission and autophagy. These processes rely on the collaboration of a variety of key proteins in the inner and outer membranes of mitochondria to jointly regulate the morphological structure and functional integrity of mitochondria, repair mitochondrial damage, and maintain the homeostasis of their internal environment. The imbalance of mitochondrial quality control is associated with leukemia. Therefore, by exploring the mechanisms related to mitochondrial quality control of various leukemia cells and their interactions with immune cells and immune microenvironment, this article sought possible targets in the treatment of leukemia, providing new ideas for the immunotherapy of leukemia.
Mouse animal models are the most commonly used experimental tools in scientific research, which have been widely favored by researchers. The animal model of mouse leukemia appeared in the 1930s. During the past 90 years, researchers have developed various types of mouse leukemia models to simulate the development and treatment of human leukemia in order to promote effectively the elucidation of the molecular mechanism of leukemia' development and progression, as well as the development of targeted drugs for the treatment of leukemia. Considering that to myeloid leukemia, especially acute myeloid leukemia, there currently is no good clinical treatment, it is urgent to clarify its new molecular mechanism and develop new therapeutic targets. This review focuses on the various types of mouse models about myeloid leukemia used commonly in recent years, including mouse strains, myeloid leukemia cell types, and modeling methods, which are expected to provide a reference for relevant researchers to select animal models during myeloid leukemia research.
Objective To assess the clinical effectiveness and safety of inductive treatment with arsenic trioxide （As203） for acute promyelocytic leukemia （APL）. Methods Randomized controlled trials （RCTs） were identified from MEDLINE （1966 -July, 2005 ）, EMBASE （1984 -July, 2005 ）, The Cochrane Library （ Issue 3, 2005） and CBM- disc （1978 -July, 2005）. The references of eligible studies were handsearched. RCTs of As203 treating for APL were included. Data were evaluated and extracted by two reviewers independently with designed extraction form. RevMan 4. 2.7 software was used for data analysis. Results Six RCTs involving 323 patients were included. Two studies reported that there was no statistical difference between As2O3 group and all-transretinoic acid （ATRA） group in mortality for patients with APL or APL patients with complications of desseminated intiavascular coagulation or cerebra hemorrhage. The pooled result of 4 studies showed that there was no statistical difference with RR 0.98, 95 % CI 0.86 to 1.12 in complete remission （CR） rates between the two groups. The result of one study showed that the CR rate of patients with intravenous injection of As203 in 2 divided dosages with longer injection duration was higher with RR 1.31, 95% CI 0.86 to 1.12 compared with those with a single intravenous injection. Adverse effects in As2O3 group were less than ATRA group. Conclusions Inductive treatment with As2O3 for acute promyelocytic leukeuia has similar mortality and CR with less adverse effects compared with ATRA. More trials of high quality are required.
Objective To systematically review the health economic evaluation studies of medicines for the treatment of acute myeloid leukemia (AML). MethodsThe PubMed, EMbase, Cochrane Library, CBM, CNKI, and WanFang Data, as well as the CRD database specifically for health economics were electronically searched from inception to June 2022, and related journals in the field of health economics and the websites of HTA institutions in various countries were manually searched. The quality of the studies was assessed using the CHEERS checklist. The basic characteristics of health economics evaluation publications were summarized, the quality of model structures and methodologies was assessed and economic evaluation results were compared among different treatments. Results A total of 17 studies were included, and cost-effectiveness analyses were conducted from the perspectives of the health system, patients, the whole society, and medical insurance payers. The economic evaluation models were relatively unified, but there were differences in methods and results reporting, and the quality needed to be improved. The research objects were mainly the comparison of hypomethylating agents, targeted medicine and traditional chemotherapy regimens, as well as the comparison of different chemotherapy combinations and different drug dosages. Conclusion Real-world studies are mainly focused on traditional chemotherapy regimens, and model-based health economic evaluations, such as Markov models, are more frequently applied to newly developed targeted drugs and demethylation drugs. Among all treatments, the chemotherapy regimens including cytarabine, midostaurin, and decitabine are found to be more cost-effective.
Objective To investigate the expression of Bcl-2 in acute leukemia of different pathological states and its relationship with chemotherapeutic efficacy. Methods Case-control studies and cohort studies were collected by searching the electronic bibliographic databases such as CBMdisc (1979 to 2010), Chinese Sic-tech Periodical Full-text Database (1989 to 2010), WanFang (1982 to 2010), Chinese Journals Full-text Database (since 1994), China Master’s Theses Full-text Database (since 1999), and China Doctor Dissertations Full-text Database (since 1999). All the relevant studies were identified and the quality of the included studies was assessed. The RevMan 5.0 software was used for meta-analysis. Results A total of 10 studies were included. The results of meta analyses showed: the complete remission of acute leukemia with Bcl-2 positivity was lower than that of the Bcl-2 negative patients after chemotherapy and the difference between them was significant (OR=0.26, 95%CI 0.14 to 0.46); the difference between acute lymphocytic leukemia and acute non-lymphocytic leukemia in terms of Bcl-2 positive rate was not significant (OR=0.87, 95%CI 0.46 to 1.65); the Bcl-2 positive rate in complete remission (CR) patients after chemotherapy was significantly lower than that of partial remission (PR) and none remission (NR) patients (SMD= –0.87, 95%CI –1.53 to –0.20, P=0.01). Conclution The current domestic evidence proves that Bcl-2 is significantly correlated with the remission rate of acute leukemia patients, but more high-quality studies are still needed.
ObjectiveTo investigate the relationship between the expressions of B-cell-specific monoclonal leukemia virus insert site 1 (Bmi1) and human telomerase reverse transcriptase (hTERT) genes and the proliferative capacity of stem cells. MethodsCord blood CD34+ cells were cultured in IMDM medium containing fetal bovine serum, stem cell growth factor, thrombopoietin, and Fms-like tyrosine kinase 3 ligand during a 28-day ex vivo expansion process, while the expansion fold, specific growth rate, and the colony-forming efficiency were monitored. Then the Bmi1 and hTERT mRNA expressions in CD34+ cells were detected by fluorescence quantitative PCR, and the relations between the expressions and the cell proliferative capacity were analyzed. ResultsCD34+ cells expanded (20.1 ± 3.5) folds during the 28-day culture, while the proportion declined from 95.5% ± 2.6% before culture to 2.1% ± 0.4%. Both the specific growth rate and colony-forming efficiency of CD34+ cells declined significantly after 7 days, while the expression levels of Bmi1 and hTERT mRNA in CD34+ cells reached top at 7 days and declined gradually thereafter. ConclusionThe expressions of Bmi1 and hTERT genes may have a close relation to the proliferative capacity of CD34+ cells.
Objectives To systematically review the relationship between indoor decoration and childhood leukemia in China. Methods CNKI, WanFang Data, VIP, CBM, PubMed, EMbase and The Cochrane Library databases were electronically searched to obtain case-control studies of the relationships between indoor decoration and childhood leukemia from inception to December 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 13 studies involving 1 727 cases and 2 468 controls were included. The results of meta-analysis showed that indoor decoration could increase the risk of childhood leukemia in China (OR=2.69, 95%CI 1.82 to 3.98, P<0.000 01). Conclusions The current evidence suggests that indoor decoration is a risk factor for childhood leukemia in Chinese. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify above conclusions.
Objective To assess the clinical effectiveness and safety of fludarabine and cyclophosphamide (FC) combined with rituximab chemotherapy regimen (FCR regimen) for patients with chronic lymphoblastic leukemia (CLL). Methods The databases such as PubMed, The Cochrane Library, SpringerLink, CNKI, and CBM were searched from 2000 to 2011. The randomized controlled trials (RCTs) on FC regimen versus FCR regimen for CLL were retrieved. The methodological quality of the included studies was assessed according to the Cochrane Reviewer’s Handbook, and meta-analyses were performed using RevMan 5.0 software. Results Three RCTs involving 1 623 patients with CLL were included. The results of meta-analyses showed that significant differences were found in the progression-free survival (PSF)(Plt;0.001), overall response (OR=1.94, 95%CI 1.49 to 2.53, Plt;0.000 01), complete remission (OR=2.54, 95%CI 2.00 to 3.22, Plt;0.000 01), and grade III or IV neutropenia (OR=1.60, 95%CI 1.33 to 1.92, Plt;0.000 01); but no significant differences were found in the partial response (OR=0.74, 95%CI 0.35 to 1.55, P=0.43), grade III or IV thrombocytopenia (OR=0.97, 95%CI 0.74 to 1.27, P=0.83) and autoimmune hemolytic anemia (OR=0.86, 95%CI 0.59 to 1.27, P=0.45) between FCR and FC regimen. Conclusion The FCR regimen can improve the progression-free survival, overall response and complete remission. Meanwhile, it sometimes increases the incidence of Grade III or IV events, such as neutropenia, thrombocytopenia, autoimmune hemolytic anemia and nausea and vomiting.
Objective To explore the prognostic value of red cell volume distribution width (RDW) for hematological malignancies. Methods PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chongqing VIP, and SinoMed were searched for related literatures on myelodysplastic syndrome, leukemia and other hematological malignancies and pretreatment RDW from the establishment of databases to April 5, 2022. The main statistical indicators were Hazard ratio (HR) and its 95% confidence interval (CI). Stata 12.0 SE software was used for analysis, and Q test was used to evaluate literature heterogeneity. Subgroup pooled analysis was used to evaluate the prognostic value of RDW. Results A total of 7 articles were included, with a total of 804 patients. A fixed-effect model was selected for meta-analysis, and the results showed that patients with elevated pretreatment RDW had worse overall survival [HR=2.91, 95%CI (2.01, 4.22), I2=0%, P=0.714]. The results of subgroup analysis for different types of diseases showed that in myelodysplastic syndrome group [HR=2.61, 95%CI (1.28, 5.31), I2=22.0%, P=0.258)], chronic myeloid leukemia group [HR= 3.24, 95%CI (1.91, 5.51), I2=0%, P=0.546], and adult T-cell leukemia/lymphoma group [HR=2.64, 95%CI (1.22, 5.70)], the overall survival rate of patients with elevated pretreatment RDW were worse. Sensitivity analysis showed that the study was stable and there was no heterogeneity in the overall study result.Conclusion Elevated pretreatment RDW is associated with overall survival and can be used as an indicator for evaluating the prognosis of hematological malignancies, but large sample studies are still needed to determine the best predictive cutoff for various diseases.
Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) is a malignancy of mature B cells characterized by progressive lymphocytosis, lymphadenopathy, and splenomegaly. On February 21st 2019, with the accumulating of new data, the National Comprehensive Cancer Network updated the guideline for CLL/SLL. This article aims at providing a reasonable interpretation of the most important messages conveyed in the guideline.