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Capone, S.

Publications and source records attributed to Capone, S..

2 recordsLinked to original sources

A previously missed population of antigen-specific CD8 T cells divides in the blood after vaccination

Although clonal expansion is a hallmark of adaptive immunity, the location(s) where antigen-responding T cells enter cell cycle and complete it have been poorly explored. This lack of knowledge stems partially from the limited experimental approaches available. By using Ki67 plus DNA staining and a novel data analysis technique, we distinguished antigen-specific CD8 T cells in G0, in G1, and in S-G2-M phases after intramuscular vaccination of BALB/c mice with antigen-expressing viral vectors. We discovered an entire population of cycling cells that are usually missed. This \"extra\" population was present early after vaccination in lymph nodes, spleen and, surprisingly, also in the blood, which is not expected to be a site for mitosis of normal non-leukemic cells. These results have implications for previous and future immunological studies in animal models, and potentially in humans. They might also inspire hematologists to seek for other missed populations of dividing cells in blood.

immunology

Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions

We present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Childrens Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, miRNA sequencing and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including novel gene fusions and focal MBNL1, ZEB2, and ELF1 deletions, were disproportionately prevalent in young as compared to adult patients. Conversely, DNMT3A and TP53 mutations, common in adults, are conspicuously absent from virtually all pediatric cases. Novel GATA2, FLT3, and CBL mutations, recurrent MYC-ITD, NRAS, KRAS, and WT1 mutations are frequent in pediatric AML. Deletions, mutations, and promoter DNA hypermethylation convergently impact Wnt signaling, Polycomb repression, innate immune cell interactions, and a cluster of zinc finger genes associated with KMT2A rearrangements. These results highlight the need for, and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.

cancer biology