Acute myeloid leukemia (AML) is a malignant hematological disease caused by the abnormal hematopoietic system. Its specific pathogenesis is still unclear. Therefore, we have carried out a series of related studies. Firstly, co-expression analysis of acute myeloid leukemia related genes in the Human Mendelian Genetic Database (OMIM) was carried out, and a co-expression module was constructed. Further enrichment analysis of module-related genes with Go and KEGG was carried out. Subsequently, the modules are analyzed by Crosstalk to show their interaction. Also, pivot prediction is used to identify critical factors in the regulatory module and potential target drugs. Results A total of 14 co-expression modules were obtained, which were found to be significantly involved in cell proliferation and apoptosis, Ras and Wnt signaling pathways. The modules with higher connectivity (UBB, RAC1, TP53, PIK3CA) were also counted. Also, it is found that there is significant crosstalk between these modules. On the other hand, we screened 2815 drivers of regulatory modules, including TP53, E2F1, MYC-based transcription factors, and non-coding RNA (ncRNA) dominated by microRNA-320a, microRNA-193b-3p, and microRNA-93-5p. Finally, many regulatory drugs (Copper, Artenimol, Indomethacin, etc.) with targeted pathogenic genes were predicted. Overall, this study explores the underlying pathogenesis of acute myeloid leukemia and predicts the related regulatory drugs. The results of this study provide a new method and theoretical basis for follow-up mechanism research and treatment strategy.

Background:The cause of hepatitis B virus (HBV) reactivation in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) is unclear. Aims: Taiwan has a high prevalence of HBV infection, and this study aimed to investigate the epidemiology of HBV reactivation in patients with CML treated with TKIs. Methods: We retrospectively reviewed 175 adult patients with CML who were treated using TKIs at National Taiwan University Hospital between January 2008 and July 2018. HBV infection status and reactivation were reviewed during follow-up. Results: A total of 99 men and 76 women with a median age of 46 years (range: 18-97) were enrolled in this study. Twenty-one (12%) of 175 patients were carrying HBV when they were diagnosed with CML. Eight HBV carriers were prophylactically treated using an antiviral agent, and the others were closely followed-up. At a median follow-up period of 41 months (range 1-129 months), 6 (28.6%) of the 21 HBV carriers had 7 episodes of HBV reactivation. Two (1.3%) of the 154 negative hepatitis B surface antigen (HBsAg) patients had reverse seroconversion and became positive HBsAg, and both patients had acute blastic transformation and allogeneic transplantation. A univariate analysis revealed positive HBsAg and negative anti-Hepatitis B surface antibodies (anti-HBs Ab) significantly correlated with HBV reactivation. In this retrospective cohort study, the incidence of HBV reactivation was 0.5 per 100 person-years in patients with CML carrying HBV who had been treated with TKIs and 0.076 per 100 person-years in all patients with CML treated with TKIs. Summary/Conclusion: HBV reactivation could develop in patients with CML treated with TKI, especially in those who are HBV carriers. The incidence is lower than it is in hematological patients with HBV carrier status who have been treated with chemotherapy, immunotherapy and stem cell transplantation. We suggest that all patients with CML with positive HBsAg undergo prophylaxis with an antiviral agent. The cause of HBV reactivation in patients with resolved HBV infection and no allogeneic transplantation is unclear, and although the risk is low, further investigation is required.