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.
ObjectiveTo explore the risk factors of nosocomial infection in children with acute lymphoblastic leukemia during induction remission chemotherapy.MethodsThe children with acute lymphoblastic leukemia who were admitted to the Department of Pediatrics, Huai’an First Hospital Affiliated to Nanjing Medical University between December 2012 and December 2018 were divided into the infection group (including the severe infection subgroup and the non-severe infection subgroup) and the non-infection group according to whether nosocomial infection occurred during induction and remission chemotherapy. The clinical data of patients were collected. Univariate analysis and multivariate logistic regression were used to analyze the risk factors of nosocomial infection during induction remission chemotherapy in children with acute lymphoblastic leukemia.ResultsA total of 96 patients were included. There were 67 cases in the infection group (26 in the severe infection subgroup and 41 in the non-severe infection subgroup) and 29 cases in the non-infection group. Univariate analysis showed that the granulocyte deficiency time and the prevalence of skin and mucosal damage in the infection group were significantly higher than those in the non-infection group, and the infection group had significantly lower laminar bed use and serum albumin level than the non-infection group did (P< 0.05). Multivariate logistic regression analysis showed that prolonged agranulocytosis [odds ratio (OR)=23.075, 95% confidence interval (CI) (3.682, 144.617), P=0.001], skin and mucosal lesions [OR=12.376, 95%CI (1.211, 126.507), P=0.034], hypoalbuminemia [OR=5.249, 95%CI (1.246, 22.113), P=0.024] were independent risk factors for nosocomial infection during induction and remission of childhood acute lymphoblastic leukemia, while laminar bed [OR=0.268, 95%CI (0.084, 0.854), P=0.026] was the protective factor.ConclusionsLong-term agranulocytosis, skin and mucosal lesions, and hypoalbuminemia are independent risk factors for nosocomial infection in children with acute lymphoblastic leukemia during induction remission chemotherapy. Laminar flow bed is its protective factor.
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.
Objective To investigate the clinical features, diagnosis and treatment of symptomatic epilepsy complicated with central nervous system leukemia (CNSL) recurrence after acute lymphoblastic leukemia (ALL) treatment in children. MethodsThe clinical data of a child with secondary recurrence of CNSL complicated with symptomatic epilepsy after ALL treatment admitted to the Department of Pediatrics of the Second Affiliated Hospital of Auhui Medical University from December 2020 to February 2023 were retrospectively analyzed, and the relevant literature was reviewed and discussed. ResultsPatient was ALL for nealy two years after treatment in the central nervous system leukemia relapse of concurrent symptomatic epilepsy, two of the central nervous system leukemia relapse when starting symptoms are seizure, the first recurrence was status epilepticus, second recurrence of concurrent limb hemiplegia symptoms, cerebrospinal fluid, cranial magnetic resonance (MRI) and abnormal changes of electroencephalogram and clinical features, the abnormal changes of brain MRI lesions and electroencephalogram did not disappear. Chemotherapy, intrathecal injection and radiotherapy were given for the primary treatment, follow up CAR-T immunotherapy, and the treatment was successively combined with nalproate and levetiracetam. Currently, the seizures were controlled. ConclusionFor children with ALL, the recurrence of CNSL should be warned after the end of treatment. Cerebrospinal fluid, cranial imaging and electroencephalogram examination should be completed in time to confirm the diagnosis. If the crania imaging lesions persist after treatment and abnormal electroencephalogram discharge does not disappear, the possibility of CNSL recurrence should be warned when the epileptic seizures are repeated. On the basis of primary disease active treatment, combination of antiseizure medications is preferable.
Continuous activation of Janus kinase (JAK)- signal transduction and activator of transcription (STAT) signaling pathway is prevalent in leukemia cells, and it has been found that this pathway plays an important role in acute leukemia (AL). JAK2/JAK1 gene mutations are found in both acute myelocytic leukemia and acute lymphoblastic leukemia and may have implications for the treatment and overall prognosis of the disease. Among the STAT family members, STAT3 and STAT5 proved to be key factors in AL. These gene mutations may provide new targets and new ideas for the treatment of AL. This article provides a review of the research progress of JAK-STAT signaling pathway, related gene mutations and AL.
ObjectiveTo systematically review the efficacy and safety of different tyrosine kinase inhibitors (TKIs) in the treatment of chronic myelocytic leukemia (CML).MethodsPubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of nilotinib, dasatinib, flumatinib and imatinib for CML from inception to August, 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; network meta-analysis was then performed using Stata 15.0 software and R 3.4.0 software.ResultsA total of 8 RCTs involving 2 775 patients were included. Compared with other TKIs, flumatinib had higher 3-month early molecular response and 1-year progression free survival, and the incidence of serious side effects was relatively low. Major molecular response and complete cytogenetic response were significantly superior to imatinib, and had the same or similar effects to other second-generation TKIs.ConclusionsCurrent evidence shows that flumartinib in the treatment of CML is obviously superior to imatinib, has the same or similar effect with other second generation TKIs. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusions.
Interferon regulatory factor 4 (IRF4) is one of the transcription factors in the interferon regulatory factor family. In the normal physiological process, IRF4 protein is a key factor regulating B cell development, such as early B cell development, pre-B cell switch recombination, mature B cell somatic hypermutation, and also a key factor regulating plasma cell differentiation. In addition, in recent years, it has been reported that Irf4 gene abnormalities or abnormal protein expression is closely involved in the occurrence and development of a variety of B cell or plasma cell tumors. This article reviews the physiological role of IRF4 in the differentiation and maturation of B cell or plasma cells, how IRF4 participates in the occurrence and development of B cell or plasma cell tumors, and its potential therapeutic target for B cell or plasma cell tumors.