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.
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 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.
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.
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.
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 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 systematically review the effectiveness and safety of arsenic trioxide (ATO) versus retinoic acid for patients with acute promyelocytic leukemia (APL). Methods Such databases as PubMed, The Cochrane Library (Issue 12, 2012), CNKI, WanFang Data and VIP were electronically and comprehensively searched from inception to December 2012, for randomized controlled trials (RCTs) on the effectiveness and safety of ATO versus retinoic acid for patients with APL. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.0.2 software. Results Eight RCTs involving 586 cases of APL patients. The results of meta-analysis showed that, ATO and all-trans-retinoic (ATRA) were not statistically different in CR rates (OR=0.85, 95%CI 0.54 to 1.35, P=0.50), CR time (OR=–8.14, 95%CI –16.42 to 0.13, P=0.05), recurrence rates (OR=0.14, 95%CI 0.02 to 1.21, P=0.07), early mortality (OR=0.82, 95%CI 0.32 to 2.06, P=0.67), and five-year total survival rates (OR=1.19, 95%CI 0.54 to 2.60, P=0.66). ATO had lower incidences of adverse reaction such as hyperleukocytosis syndrome (OR=0.32, 95%CI 0.18 to 0.58, P=0.000 1) and retinoic acid syndrome (OR=0.05, 95%CI 0.02 to 0.14, Plt;0.000 01). Conclusion ATO and ATRA are alike in CR rates, CR time, recurrence rates, early mortality, and five-year total survival rates, but ATO causes less adverse reaction. Due to the limited quantity and quality of the included studies, ATO should be applied with caution according to patients’ conditions in clinic.
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.
