Haematological cancer articles within Nature

Featured

  • Outlook |

    Despite its rarity, multiple myeloma is an ideal testing ground for cancer biology, says William Matsui.

    • William Matsui

  • Outlook |

    Drugs introduced to fight multiple myeloma in the past decade have revolutionized treatment and extended patients' lives. Are the improvements set to continue?

    • Adrianne Appel

  • Outlook |

    In the fight against myeloma, researchers are investigating its interactions with molecular neighbours in the bone marrow.

    • Virginia Hughes

  • Outlook |

    New technology to peer into the bones could help improve the treatment of multiple myeloma patients.

    • Cassandra Willyard

  • Outlook |

    Multiple myeloma begins with a benign condition before progression to full-blown cancer, and work is underway to uncover the origins of both.

    • Cynthia Graber

  • Outlook |

    Finding a treatment for the bone destruction caused by myeloma helped researchers understand the biology of bone.

    • Jennifer Berglund

  • Outlook |

    Stem-cell transplants are an important tool for treating myeloma. But with improved drug alternatives, doctors disagree about the best time to give the treatment.

    • Elie Dolgin

  • News & Views |

    Mutations that lead to increased activity of the Notch signalling pathway are well defined in human cancer. New work implicates decreased activity of this pathway in a type of blood cancer. See Letter p.230

    • Demetrios Kalaitzidis
    •  & Scott A. Armstrong

  • Article
    | Open Access

    Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.

    • Michael A. Chapman
    • , Michael S. Lawrence
    •  & Todd R. Golub

  • Letter |

    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

  • Article |

    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.

    • Laura Pasqualucci
    • , David Dominguez-Sola
    •  & Riccardo Dalla-Favera

  • Letter |

    Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.

    • Christian Steidl
    • , Sohrab P. Shah
    •  & Randy D. Gascoyne

  • Letter |

    Misrepair of DNA double strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin and T-cell receptor loci has been implicated in the pathogenesis of lymphoid malignancies. Here, the RAG2 carboxy terminus is shown to be critical for maintaining genomic stability. Rag2c/c p53−/− mice, unlike Rag1c/c p53−/− and p53−/− mice, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. These results reveal a new 'genome guardian' role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2c/c p53−/− and Atm−/− mice.

    • Ludovic Deriano
    • , Julie Chaumeil
    •  & David B. Roth

  • Letter |

    This is one of two papers demonstrating that in several cancer types including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by the FBW7 tumour suppressor. This study finds that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors. Deletion or mutation of FBW7 found in cancer patients therefore can render tumours resistant to these therapies.

    • Hiroyuki Inuzuka
    • , Shavali Shaik
    •  & Wenyi Wei

  • Letter |

    Recruitment of 53BP1 to double-strand DNA breaks is an important step in the cellular response to DNA damage. Here, the histone methyltransferase MMSET is shown to be responsible for localized increases in a histone modification that is involved in recruiting 53BP1. The mechanism of MMSET recruitment to DNA damage sites is also investigated.

    • Huadong Pei
    • , Lindsey Zhang
    •  & Zhenkun Lou

  • Article |

    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

  • Letter |

    This study finds frequent mutations in MYD88 in the activated B-cell-like subtype of diffuse large B-cell lymphoma and, with lower frequency, in mucosa-associated lymphoid tissue lymphomas. MYD88 mediates signalling by Toll-like receptors, and the mutations, most of which affect the same amino acid, are shown to activate the pathway and promote cancer cell survival.

    • Vu N. Ngo
    • , Ryan M. Young
    •  & Louis M. Staudt

  • Article |

    Analysing single cells from human B-cell acute lymphoblastic leukaemias, this study maps the genetic heterogeneity of cells within a given tumour sample, the evolutionary path by which different subclones have emerged, and ongoing dynamic changes associated with relapse. Leukaemia-propagating 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-propagating cells.

    • Kristina Anderson
    • , Christoph Lutz
    •  & Mel Greaves

  • Letter |

    The TET family of enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Mutations in the gene encoding TET2 are frequently observed in myeloid malignancies. Here it is shown that these disease-associated mutations compromise TET2 catalytic activity; bone marrow samples from patients with TET2 mutations have low levels of 5hmC in genomic DNA, and TET2 is required for normal haematopoietic differentiation. Measurement of genomic 5hmC levels may prove valuable as a diagnostic tool in myeloid cancers.

    • Myunggon Ko
    • , Yun Huang
    •  & Anjana Rao

  • Letter |

    Cell cycle checkpoints, such as the S-phase checkpoint, delay cell division to give the cell time to repair any damaged DNA. Here it is shown that the MLL gene — frequently disrupted in leukaemia — is part of the S-phase checkpoint. When DNA is damaged, MLL is phosphorylated by the ATR protein, causing MLL to accumulate on chromatin and methylate histone H3 on lysine 4. This delays DNA replication. MLL translocations, such as those that occur in leukaemia, disrupt this pathway and cause genomic instability.

    • Han Liu
    • , Shugaku Takeda
    •  & James J.-D. Hsieh

  • Letter |

    One model for cancer development posits that the proliferating cells in a tumour can become 'addicted' to activating mutations in an oncogene. With the realization that certain microRNAs promote tumorigenesis, it has been proposed that tumours may also become dependent on such 'oncomiRs'. Here, evidence is provided that the gene encoding microRNA-21 is an oncogene, and that in its absence, tumours undergo apoptosis and regress. Thus tumours can indeed become addicted to oncomiRs.

    • Pedro P. Medina
    • , Mona Nolde
    •  & Frank J. Slack

  • Letter |

    Chronic myelogenous leukaemia (CML) can progress from a chronic to an acute phase. These authors show in mouse models that leukaemia progression is controlled by the cell-fate regulator Musashi2, which in turn regulates Numb, Notch and p53 to block cellular differentiation. Musashi2 expression can be increased by aberrant transcription factors found in leukaemia, is observed during cancer progression in human CML patients and is associated with poorer prognosis.

    • Takahiro Ito
    • , Hyog Young Kwon
    •  & Tannishtha Reya

  • Letter |

    The four receptors of the Notch family are transmembrane proteins through which mammalian cells communicate to regulate cell fate and growth. Aberrant signalling through each receptor has been linked to disease, so the Notch pathway is a compelling drug target. But current drugs cannot distinguish between the different Notch proteins. Here, phage display technology has been used to generate highly specialized antibodies, enabling the functions of Notch1 and Notch2 to be discriminated in humans and mice.

    • Yan Wu
    • , Carol Cain-Hom
    •  & Christian W. Siebel

  • 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 |

    Chronic myeloid leukaemia is caused by a BCR-ABL fusion, a constitutively active tyrosine kinase that, it is believed, leads to suppression of the forkhead O transcription factors (FOXO). Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Foxo3a is now shown to have an essential role in the maintenance of CML LICs in a mouse model.

    • Kazuhito Naka
    • , Takayuki Hoshii
    •  & Atsushi Hirao

  • Letter |

    The role of B-cell-receptor (BCR) signalling in human B cell lymphomas has been a long-standing question, with genetic and functional evidence for its oncogenic role in human lymphomas lacking. Here, a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like subtype of diffuse large B-cell lymphoma is described and analysed, with potential implications for future therapeutic strategies.

    • R. Eric Davis
    • , Vu N. Ngo
    •  & Louis M. Staudt

Browse broader subjects

Browse narrower subjects

Browse Haematological cancer across other nature.com journals