Cells forming malignant tumors are distinguished from those forming normal tissues based on several features: accelerated/dysregulated cell division, disruption of physiologic apoptosis, maturation/differentiation arrest, loss of polarity, and invasive potential. Among them, accelerated cell division and differentiation arrest make tumor cells similar to stem/progenitor cells, and this is why tumorigenesis is often regarded as developmental reversion. Here, in addition to developmental reversion, we propose another insight into tumorigenesis from a phylogeny viewpoint. Based on the finding that tumor cells also share some features with unicellular organisms, we propose that tumorigenesis can be regarded as “evolutionary reversion”. Recent advances in sequencing technologies and the ability to identify gene homologous have made it possible to perform comprehensive cross-species transcriptome comparisons and, in our recent study, we found that leukemic cells resulting from a polycomb dysfunction transcriptionally resemble unicellular organisms. Analyzing tumorigenesis from the viewpoint of phylogeny should reveal new aspects of tumorigenesis in the near future, and contribute to overcoming malignant tumors by developing new therapies.
The utility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from sources other than matched related donors (alternative donors) in the management of elderly acute myeloid leukemia (AML) patients in first complete remission (CR1) has not been clarified. To investigate the benefit of allo-HCST in the management of elderly AML patients in CR1, we retrospectively collected data from consecutive AML patients aged 60-66 years, who had been diagnosed between 2000 and 2014 and achieved CR. A total of 43 patients were included in this study, and 12 patients received allo-HSCT in CR1 only from alternative donors. Compared to chemotherapy alone, allo-HSCT improved overall survival (OS) (P=0.050) and cumulative incidence of relapse (CIR) (P=0.0059) in univariate analysis. OS and CIR at 3 years from CR1 were 82.5% vs 34.2%, and 17.5% vs 74.6%, respectively. In multivariate analysis, allo-HSCT also improved OS (hazard ratio (HR), 0.18; 95% confidence interval (CI), 0.039-0.80) and CIR (HR, 0.090; 95% CI, 0.029-0.28). Allo-HSCT from an alternative donor is a credible option in the treatment of elderly AML patients in CR1.
Although fatal pulmonary complications frequently occur during the course of acute leukemia, a minor proportion of the complications are due to leukemia itself. Infections, drug reactions and concomitant medical conditions are the major causes of respiratory distress in leukemic patients. We treated four patients with acute myeloid leukemia complicated by leukemic cell lysis pneumopathy (LCLP). All of the patients had leukemia of monocytoid origin and their respiratory function deteriorated soon after chemotherapy initiation. Although two of the patients required mechanical ventilation, all four improved after continued chemotherapy. Our experience indicates that, in cases of LCLP, chemotherapy should be continued with maximal respiratory support.
During thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer E
