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Showing 1–7 of 7 results
Advanced filters: Author: Letha A Phillips Clear advanced filters

  • This paper reports the identification of high-frequency deletions in the Ikaros gene in acute lymphoblastic leukaemia cases that are characterized by BCR-ABL1 translocations. In contrast, BCR-ABL1 CML is not associated with Ikaros deletions in chronic phase patients, but are often acquired during progression to blast crisis. These deletions lead to expression of altered transcripts. In contrast to previous models suggesting that these transcripts result from aberrant alternative splicing, it is shown that the deletions found are due to aberrant RAG-mediated recombination.

    • Charles G. Mullighan
    • Christopher B. Miller
    • James R. Downing
    Research
    Nature
    Volume: 453, P: 110-114

  • Analysing human B-cell acute lymphoblastic leukaemias, this study maps the genetic heterogeneity of cells within a given tumour sample and the evolutionary path by which different subclones have emerged. Leukaemia-initiating cells that transplant the disease mirror the genetic variegation of the bulk tumours, providing insights into the heterogeneity of these functional subpopulations at the genetic level. This has implications for therapeutic approaches targeting the tumours and specifically leukaemia-initiating cells.

    • Faiyaz Notta
    • Charles G. Mullighan
    • John E. Dick
    Research
    Nature
    Volume: 469, P: 362-367

  • George Daley and colleagues show that Lin28 and Lin28B promote cellular transformation by repressing let-7 family members, leading to derepression of let-7 targets. They also find that LIN28 and LIN28B are overexpressed in ∼15% of primary human tumors and cancer cell lines and that their expression is associated with aggressive disease and poor prognosis across multiple tumor types.

    • Srinivas R Viswanathan
    • John T Powers
    • George Q Daley
    Research
    Nature Genetics
    Volume: 41, P: 843-848

  • In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.

    • Charles G. Mullighan
    • Jinghui Zhang
    • James R. Downing
    Research
    Nature
    Volume: 471, P: 235-239