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 search evidence in the treatment of Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL) for guiding chnical practice. Methods We searched MEDLINE (February, 1970~July, 2005 ) and SUMSEAILCH (till July, 2005 )to identify systematic reviews(SIL), randomized controlled trials(RCTs) and controlled clinical trials (CCTs) in the treatment of Ph-positive ALL. Results One RCT and 8 CCTs were identified. The results showed that Ph-positive ALL had a very poor prognosis . Chemotherapy and bone marrow transplantation (BMT) were the two main ways to treat the disease. Outcome of conventional chemotherapy treatment for adults with the disease was poor. Outcome of treatment with hyper-CVAD and imatinib mesylate was better and BMT was the only way which could potentially cure the disease. Conclusions Treatment of Ph-positive ALL with hyper-CVAD and imatinib mesylate may induce higher remission rate and disease free survival rate. BMT is the best way to cure the disease.
Objective To apply the evidence-based treatment method to direct the clinical therapy of refractory chronic lymphocytic leukemia (CLL). Methods Such evidence-based medicine databases as The Cochrane Library (Issue 10, 2010), OVID database, PubMed (January 1992 to October 2010) and http://www.nccn.org/ were searched to find the clinical evidence with high quality and the optimum treatment was designed based on the patient’s preferences. Results Two RCTs and five CCTs were included. The available clinical evidence displayed that rituximab could improve the therapeutic effect of combined chemotherapy on the refractory CLL, the COP/CHOP regimens were effective for the fludarabine-resistant CLL, and hematopoietic stem cell transplantation could be an effective salvage therapy for the relapsed/refractory CLL, but not the first-line recommendation drug. This patient was treated by CHOP regimen combined with rituximab, the condition of disease was improved two months after stopping chemotherapy, and the follow-up was conducted. Conclusion Current evidence reveals that rituximab combined with CHOP regimen produces good tolerance with a better clinical outcome than that of CHOP regimen. Clinical practice results display that the combination of rituximab and CHOP regimen can bring good prognosis to the patient, but still needs high-quality evidence to prove.
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.
ObjectiveTo explore the clinical features and outcomes of relapsed acute lymphoblastic leukemia (ALL) in children. MethodsThirty-two ALL children treated in line with the Chinese Child Leukemia Cooperative Group ALL-2008 protocol with a relapse of the disease during January 2009 to May 2013 were enrolled into this study. Their clinical features and outcomes were retrospectively analyzed and compared with those who achieved continuous complete remission (CCR). ResultsThere were 32 relapsed cases among 319 newly diagnosed ALL cases (excluding infantile ALL) during the study period, with a relapse rate of 10%. In the relapse group, the proportions of patients with peripheral blood white blood cell count ≥50×109/L at diagnosis, positive BCR/ABL fusion gene, poor prednisone response, high risk stratification, and who failed to achieve bone marrow complete remission at d15 and d33 of induction chemotherapy, were significantly higher than those in the CCR group (all P<0.05). Multivariate analysis showed that high risk stratification was an independent risk factor for relapse (OR=3.529, P=0.002). In terms of site of relapse, isolated marrow relapse, isolated central nervous system relapse, isolated testicular relapse and combined relapse accounted for 23 (72%), 6 (19%), 1 (3%) and 2 (6%), respectively. As regard to the time of relapse, 26 cases (81%), 4 cases (13%) and 2 cases (6%) were categorized as very early relapse, early relapse and late relapse respectively. Twenty-four children with relapsed ALL received re-induction chemotherapy. Among them, 16 cases (67%) achieved second complete remission. Nevertheless, 9 cases ultimately suffered second relapse. ConclusionRelapse, which occurs more commonly in high risk ALL group, still remains a great challenge in clinical practice. Relapsed ALL, especially those with very early and early marrow relapse, has poor prognosis.
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 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.
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.
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.
The poor treatment effect and short survival period of patients with acute leukemia are mainly due to the lack of effective early diagnosis and treatment targets. Lipid metabolism reprogramming meets the material and energy requirements for rapid proliferation and division of tumor cells, and is associated with the invasiveness, recurrence, and chemotherapy resistance of acute leukemia. This article reviews the carcinogenic and chemotherapy resistance mechanisms of lipid metabolism reprogramming in leukemia cells, and summarizes the latest findings on targeted fatty acid metabolism pathways, aiming to provide a new perspective on the role of intracellular fatty acid metabolism in the occurrence and development of acute leukemia. It is expected to provide a theoretical basis for the elucidation of its resistance mechanism and the development of corresponding targeted therapies.