F usion genes involving ZNF384 have recently been identified in Bcell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic

Fusion genes involving have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remains unknown. We identified 16 acute lymphoblastic leukemia cases and 1 lymphoma case harboring fusions, including (n=10), (n=6) and one novel fusion. The incidence of fusions overall was 2.4% among consecutive B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of and, elevated expression was also a characteristic feature of fusions-positive patients. Mutations of , recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/μl) at presentation, and, as a result, were mostly classified as NCI high-risk. Although they responded well to steroid treatment, fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as a salvage therapy. Interestingly, relapse was frequently associated with the presence of gene deletions. Our observations indicate that fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.

Background: Sepsis and septic shock are still major causes of morbidity and mortality in spite of the availability of powerful and broadly active antibiotics. Methods: A prospective, open and randomized trial of the effect of immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis throughout a follow-up period of 28 days or until discharge, if earlier, was carried out. Ninety-eight patients were included who met at least 4 of the criteria for systemic inflammatory response syndrome due to infection. The patients were classified into three groups based on their Acute Physiology and Chronic Health Evaluation (APACHE) II score. Results: The overall survival rate was significantly improved by using PMX-F compared to the control group (41 vs. 11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more severe sepsis with an APACHE II score of 20–29, PMX-F still maintained efficacy in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not improve the survival rate in patients with an APACHE II score of greater than 30 (survival rate 7 vs. 0%) (p = 0.59). Conclusion: From these results, it is concluded that treatment with PMX-F in patients with sepsis is effective and prolongs the survival rate when applied at an early stage of sepsis. However, in severe sepsis, this therapy does not improve the survival rate.