The MLL recombinome of acute leukemias in 2017.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

Erwinia chrysanthemi strains cause death of human gastrointestinal cells in culture and express an intimin-like protein.

The bacterium Erwinia chrysanthemi is a model plant pathogen, responsible for causing cell death in plant tissue. Cell-wall depolymerizing enzymes and avirulence proteins essential for parasitism by this bacterium utilize dedicated type II and type III secretion systems, respectively. Although E. chrysanthemi is not recognized as a mammalian pathogen, we have observed that the bacterium can adhere to, cause an oxidative stress response in and kill cultured human adenocarcinoma cells. These bacteria express a surface protein that bears immunological identity to intimin, a protein required for full virulence of enterohemorrhagic and enteropathogenic Escherichia coli. A type III secretion mutant of E. chrysanthemi was observed to have a significantly lower capability of causing death than the wild-type strain in parallel cultures of human colon adenocarcinoma cells. These observations suggest that E. chrysanthemi has the potential to parasitize mammalian hosts as well as plants.