Haematological diseases

  • Article |

    A single-cell atlas of human fetal bone marrow in healthy fetuses and fetuses with Down syndrome provides insight into developmental haematopoiesis in humans and the transcription and functional differences that occur in Down syndrome.

    • Laura Jardine
    • , Simone Webb
    •  & Muzlifah Haniffa
  • Article |

    A custom adenine base editor can edit the variant of the β-globin gene that causes sickle cell disease into a non-pathogenic variant in human and mouse cells, and transplantation of the edited cells rescues sickle cell disease in mice.

    • Gregory A. Newby
    • , Jonathan S. Yen
    •  & David R. Liu
  • Article |

    Analysis of growth dynamics in a dataset from 107 patients with chronic lymphocytic leukaemia (CLL) reveals both exponential and logistic patterns of growth, which are associated with differences in genetic attributes and clinical outcomes.

    • Michaela Gruber
    • , Ivana Bozic
    •  & Catherine J. Wu
  • Letter |

    A single-cell approach is used to follow the heritable stochastic changes to DNA methylation that occur in primary chronic lymphocytic leukaemia and healthy B cells, allowing the tracing of cell lineage histories and evolution during treatment with ibrutinib.

    • Federico Gaiti
    • , Ronan Chaligne
    •  & Dan A. Landau
  • Letter |

    An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).

    • Pulin Li
    • , Jamie L. Lahvic
    •  & Leonard I. Zon
  • Letter |

    In human β-thalassaemiaerythroblasts, HSP70 is sequestered in the cytoplasm by the excess of free α-globin chains and can no longer protect the master transcriptional factor of erythropoiesis GATA-1 from caspase-3 cleavage; transduction of a nuclear-targeted HSP70 or a caspase-3 uncleavable GATA-1 mutant restored maturation of erythropoiesis.

    • Jean-Benoît Arlet
    • , Jean-Antoine Ribeil
    •  & Geneviève Courtois
  • Article |

    A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

    • Pim van der Harst
    • , Weihua Zhang
    •  & John C. Chambers
  • Letter |

    EZH2 is a methyltransferase that is mutated in lymphoma; here a potent small molecule inhibitor of EZH2 is described, which inhibits the proliferation of EZH2 mutant cell lines and growth of EZH2 mutant xenografts in mice, thus providing a potential treatment for EZH2 mutant lymphoma.

    • Michael T. McCabe
    • , Heidi M. Ott
    •  & Caretha L. Creasy
  • Letter |

    Lipid asymmetry can be disrupted during biological processes such as apoptosis, during which phosphatidylserine in the inner leaflet of the membrane is exposed on the outer membrane. It has been proposed that activation of a phospholipid scramblase catalyses bidirectional transbilayer movement of phospholipids, but the protein corresponding to this activity has not been identified. Here, the protein TMEM16F is identified, and is an essential component for the Ca2+-dependent exposure of phosphatidylserine on the plasma membrane. A patient with Scott syndrome, which results from a defect in phospholipid scrambling activity, was found to carry a mutation in the gene encoding TMEM16F.

    • Jun Suzuki
    • , Masato Umeda
    •  & Shigekazu Nagata
  • Letter |

    Disorders caused by abnormal β-globin, such as β-thalassaemia, are the most prevalent inherited disorders worldwide. For treatment, many patients are dependent on blood transfusions; thus far the only cure has involved matched transplantation of haematopoietic stem cells. Here it is shown that lentiviral β-globin gene transfer can be an effective substitute for regular transfusions in a patient with severe β-thalassaemia.

    • Marina Cavazzana-Calvo
    • , Emmanuel Payen
    •  & Philippe Leboulch
  • Article |

    A new mouse model is developed in which haematopoietic malignancies are caused by genetic changes in the microenvironment of blood cells. Deletion in bone progenitor cells of Dicer1, a gene involved in microRNA processing, leads to a myelodysplastic syndrome-like phenotype which can progress to leukaemia. Deregulation of Sbds, which is mutated in human Schwachman–Bodian–Diamond syndrome, may be involved in this process.

    • Marc H. G. P. Raaijmakers
    • , Siddhartha Mukherjee
    •  & David. T. Scadden
  • Letter |

    Worldwide, 170 million people are infected with the hepatitis C virus, which is a significant cause of liver-related illnesses and deaths. Standard treatment combines pegylated interferon alpha and ribavirin (RBV), but has some negative effects, notably RBV-induced haemolytic anaemia. Here, a genome-wide study shows that a deficiency in the enzyme inosine triphosphatase protects against haemolytic anaemia in patients receiving RBV.

    • Jacques Fellay
    • , Alexander J. Thompson
    •  & David B. Goldstein