Key Points Dnmt3a ablation in HSCs predisposes mice to develop a spectrum of myeloid and lymphoid malignancies. Dnmt3a-KO-derived myeloid malignancies and T-cell acute lymphocytic leukemia/lymphoma show distinct methylation aberrations.

DOT can be reduced by improving patient's compliance. The messaging app is useful for outpatient education and management.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-kB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-na€ ve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFb pathway activation signature.

Recent studies have indicated that the C-reactive protein/ albumin (CRP/Alb) ratio is associated with clinical outcomes in patients with hepatocellular carcinoma (HCC). We examined the prognostic value of this ratio in patients with small-cell lung cancer (SCLC). In this retrospective study, a total of 367 eligible SCLC patients were analyzed and the correlation between the pretreatment CRP/Alb ratio and overall survival (OS) was investigated. The optimal cutoff level of CRP/Alb ratio was at 0.441. A low and high CRP/Alb ratio was assigned to 65.1% and 34.9% of patients, respectively. The median OS of patients with a high CRP/Alb ratio was worse than those in the low group (13.70 vs 18.90 months HR, 1.34; p = 0.005). Disease stage (p < 0.001), performance status (PS) (p < 0.001) and pretreatment LDH (p < 0.001) were also significant predictors of OS. Multivariate analyses showed that the CRP/Alb ratio is an independent prognostic factor (p = 0.025). This study demonstrated that the CRP/Alb ratio could independently predict OS in patients with SCLC, and had comparable prognostic value to other known prognostic markers. Therefore, the CRP/Alb ratio could have prognostic value and be a measurable biomarker in patients with SCLC.

Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice.