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.
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.
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.
Objective To investigate the expression levels of fatty acid metabolism-related genes in acute myeloid leukemia (AML) and construct a prognostic risk regression model for AML. Methods Gene expression data from control groups and AML patients were downloaded from the GTEx database and The Cancer Genome Atlas (TCGA) database, followed by screening for differentially expressed genes (DEGs) between AML patients and controls. Fatty acid metabolism-related genes were obtained from the MSigDB database. The intersection of DEGs and fatty acid metabolism-related genes yielded fatty acid metabolism-associated DEGs. A protein-protein interaction network was constructed using the STRING database. Hub genes were analyzed via random forest, Kaplan-Meier survival, and Cox proportional hazards regression based on TCGA clinical data to establish a prognostic model and evaluate their diagnostic and prognostic significance. Immune cell infiltration differences between high- and low-risk groups were assessed using CIBERSORT algorithms to explore immune microenvironment variations and correlations with risk scores. Results A total of 60 fatty acid metabolism-related DEGs were identified. Further screening revealed 15 hub genes, among which four genes (HPGDS, CYP4F2, ACSL1, and EHHADH) were selected via integrated random forest, Cox regression, and Kaplan-Meier analyses to construct an AML prognostic lipid metabolism gene signature. Heatmaps demonstrated statistically significant differences in tumor-infiltrating immune cell proportions between risk groups (P<0.05). Conclusion The constructed lipid metabolism gene prognostic model may serve as a biomarker for overall survival in AML patients and provide new insights for immunotherapy drug development.
ObjectivesTo systematically review the risk of arterial ischemic and metabolic adverse events in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs).MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and VIP databases were searched to collect clinical trials, observational studies and case reports of adverse events in CML patients treated with TKIs from inception to February 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 22 studies involving 4 223 patients were included. The incidence rates of ischemic heart disease in any grade were 2 per 100 patient-years (95%CI 2 to 3) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 3) for imatinib. The incidence of ischemic heart disease in grade 3 or 4 was 1 per 100 patient-years (95%CI 0 to 2) for nilotinib. The incidence of peripheral arterial occlusive disease in any grade was 2 per 100 patient-years (95%CI 0 to 14) for nilotinib, and 0 per 100 patient-years (95%CI 0 to 2) for imatinib. The incidence of hypertension in any grade was 1 per 100 patient-years (95%CI 0 to 3) for nilotinib, and 44 per 100 patient-years (95%CI 27 to 71) for ponatinib. The incidence of hypertension in grade 3 or 4 was 2 per 100 patient-years (95%CI 0 to 15) for nilotinib, and 22 per 100 patient-years (95%CI 8 to 58) for ponatinib. The incidence of hyperlipidemia in any grade was 17 per 100 patient-years (95%CI 5 to 59) for nilotinib. The incidence of hyperglycemia in any grade was 11 per 100 patient-years (95%CI 9 to 15) for nilotinib, 2 per 100 patient-years (95%CI 1 to 4) for imatinib, 1 per 100 patient-years (95%CI 0 to 5) for dasatinib, and 19 per 100 patient-years (95%CI 19 to 20) for bosutinib. The incidence of hyperglycemia in grade 3 or 4 was 4 per 100 patient-years (95%CI 3 to 5) for nilotinib, and 1 per 100 patient-years (95%CI 1 to 2) for bosutinib.ConclusionsPatients treated with nilotinib have a greater possibility of ischemic heart and peripheral arterial occlusive disease compared with patients treated with imatinib. Patients treated with ponatinib have a high incidence rate of hypertension, and patients treated with nilotinib have a high incidence rate of hyperlipidemia. Patients treated with bosutinib and nilotinib have higher risk of hyperglycemia compared with patients treated with imatinib or dasatinib.
Objective To systematically evaluate the effectiveness of dasatinib in doses of 140 mg once daily and 70 mg twice daily for chronic myeloid leukemia (CML). Methods The randomized controlled trials (RCTs) were retrieved from Embase (1974 to November 2011), Pubmed (1966 to November 2011), The Cochrane Library (Issue 11, 2011), CBM (1979 to November 2011), VIP (1989 to November 2011), CNKI (1994 to November 2011), Wanfang Data (1997 to November 2011) and references listed in all articles. RCTs meeting inclusive criteria were included, the data were extracted, the quality was evaluated and cross-checked by two reviewers independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then meta-analyses were conducted using RevMan 5.1 software. Results A total of four studies involving two RCTs and 862 patients were included. Results of meta-analyses showed that when dasatinib was used in the long-term treatment of CML, no significant difference was found between 140 mg once daily and 70 mg twice daily in the complete hematologic response (RR=0.97, 95%CI 0.88 to 1.07, P=0.58), complete cytogenetic response (RR=0.94, 95%CI 0.80 to 1.11, P=0.47) and major cytogenetic response (RR=0.99, 95%CI 0.86 to 1.13, P=0.86). In the short-term treatment of CML, there were no significant differences in the complete hematologic response (RR=0.99, 95%CI 0.90 to 1.07, P=0.73), complete cytogenetic response (RR=0.99, 95%CI 0.78 to 1.26, P=0.95) and major cytogenetic response (RR=1.01, 95%CI 0.83 to 1.22, P=0.95). The subgroup analyses on the long-term treatment of CML in both chronic phase and advanced phase showed that there were no significant differences in the complete hematologic response, major cytogenetic response and complete cytogenetic response. Conclusion In the effectiveness of dasatinib for CML, the dose of 140 mg once daily is similar to the dose of 70 mg twice daily. Considering possible moderate selection bias existing in the methodological quality of the included studies which may affect the authenticity of outcomes, this conclusion should be further proved by conducting more high-quality, large-scale and double- blinded RCTs.
Objective To systematically evaluate the risk factors and population attributable risk of children leukemia in China, so as to provide references for policy-making. Methods The case-control studies about risk factors of children leukemia in China were searched in PubMed, CNKI, CBM, VIP and WanFang Data from inception to December 2011. According to the inclusion and exclusion criteria, two reviewers independently screened articles, extracted data, and evaluated the quality of the included studies. Then Meta-analysis was performed using STATA 11 and Excel 2003. The pooled odds ratio (OR) and 95% confidence interval (95%CI) of each risk factor were calculated, and the population attributable risk percent (PARP) based on the exposure rate of the risk factors was computed, and published bias was estimated according to the fail-safe number. Results A total of 15 case-control studies were included. The first 5 risk factors related to children leukemia were: dwelling environmental pollution (OR=2.782, 95%CI 2.268 to 3.413), house decoration (OR=2.525, 95%CI 1.736 to 3.673), maternal exposure to chemical hazards (OR=2.428, 95%CI 1.976 to 2.985), family history of tumor (OR=2.212, 95%CI 1.677 to 2.919), and child exposure to electromagnetic field around dwelling (OR=2.144, 95%CI 1.761 to 2.610). Factors with higher PARP were influenza history (37.56%), house decoration history (32.95%), X-ray exposure history (20.47%), and chemical hazards exposure history (17.37%). The fail-safe number showed the results were generally reliable. Conclusion In order to prevent and control children leukemia, positive and effective measures should be taken in the following aspects: strengthening child care, avoiding unnecessary X-ray exposure, and providing good living environment.
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 We intended to get good understanding of the current role of imatinib （or glivec） in the treatment of a patient with chronic-phase chronic myeloid leukemia. Methods We attempted to find the current best evidence of imatinib for treating chronic myeloid leukemia in chronic phase by searching ACP Journal Club （1991 -Jun, 2005 ）, The Cochrane Library（Issue 2, 2005 ）and MEDLINE（1990 -Jun, 2005 ） and further critically appraised the available evidence. Results Imatinib appeared to be more effective than current standard drag treatments in terms of hematologic and cytogenetic response with better quality of life and fewer side effects. However, there was uncertainty concerning long term outcomes. Given the current evidence together with our clinical experience and considering the patient and his family members＇ values and preference, imatinib （400 mg qd） was administered to him. No obvious adverse effects occurred with 3 months follow-up. Conclusions Imatinib is effective and well tolerated in the treatment of chronic myeloid leukemia in chronic phase. Further researches on long-term follow-up data from imatinib trials are definitely needed.