Article
|
Open Access
Featured
-
-
Article |
Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling
The potential use of circulating tumour DNA in classic Hodgkin lymphoma detection, classification and monitoring is defined.
- Stefan K. Alig
- , Mohammad Shahrokh Esfahani
- & Ash A. Alizadeh
-
Article
| Open AccessThe menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia
Revumenib, a potent and selective oral inhibitor of the menin–KMT2A interaction, is associated with a low frequency of treatment-related adverse events and promising clinical activity in patients with relapsed or refractory acute leukaemia.
- Ghayas C. Issa
- , Ibrahim Aldoss
- & Eytan M. Stein
-
Article |
Blood and immune development in human fetal bone marrow and Down syndrome
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 |
Base editing of haematopoietic stem cells rescues sickle cell disease in mice
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 |
Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells
A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.
- Erik L. Bao
- , Satish K. Nandakumar
- & Vijay G. Sankaran
-
Article |
Mouse models of neutropenia reveal progenitor-stage-specific defects
Mouse models of severe congenital neutropenia using patient-derived mutations in the GFI1 locus are used to determine the mechanisms by which the disease progresses.
- David E. Muench
- , Andre Olsson
- & H. Leighton Grimes
-
Article |
Growth dynamics in naturally progressing chronic lymphocytic leukaemia
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 |
Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia
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 |
Tracing the origins of relapse in acute myeloid leukaemia to stem cells
Identification of the cell types from which relapse arises in acute myeloid leukaemia, by following leukaemia propagation from patient-derived leukaemia samples.
- Liran I. Shlush
- , Amanda Mitchell
- & John E. Dick
-
Letter |
T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments
Here, leukaemia cells are followed by intravital microscopy as they infiltrate mouse bone marrow and respond to chemotherapy, revealing that at all stages analysed they are highly motile and do not display any associations with particular bone marrow sub-compartments.
- Edwin D. Hawkins
- , Delfim Duarte
- & Cristina Lo Celso
-
Letter |
Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment
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
-
Inside View |
Inside View: Fondation ARC
-
Letter |
HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia
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 |
Seventy-five genetic loci influencing the human red blood cell
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 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
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 |
Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function
The function of haematopoietic stem and progenitor cells is impaired by damaged DNA; here, endogenously generated aldehydes are found to be one source of such damage, which is repaired by the Fanconi anaemia pathway.
- Juan I. Garaycoechea
- , Gerry P. Crossan
- & Ketan J. Patel
-
Research Highlights |
Sisterhood of lymphoma
-
News |
Sickle-cell mystery solved
Researchers discover how carriers of the sickle-cell anaemia gene are protected from malaria.
- Meredith Wadman
-
News |
Rice seed yields blood protein
Human serum albumin from transgenic rice could ease shortages of donated blood.
- Lauren Gravitz
-
Research Highlights |
A way to save sickle cells
-
News & Views |
Alcohol, DNA and disease
Acetaldehyde, a reactive metabolite of ethanol, can damage DNA unless properly processed. A biochemical pathway involved in Fanconi anaemia seems to be essential for protection against such damage. See Article p.53
- Hans Joenje
-
Article |
Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice
- Frédéric Langevin
- , Gerry P. Crossan
- & Ketan J. Patel
-
News |
Cut-and-paste therapy fixes mouse haemophilia
All-in-one genetic repair kit treats disease inside the body.
- Janelle Weaver
-
Letter |
In vivo genome editing restores haemostasis in a mouse model of haemophilia
- Hojun Li
- , Virginia Haurigot
- & Katherine A. High
-
Letter |
Calcium-dependent phospholipid scrambling by TMEM16F
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 |
Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
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
-
Books & Arts |
Secrets of a long life
Two books on ageing understate the challenges of prolonging a healthy lifespan, finds Caleb Finch.
- Caleb Finch
-
News & Views |
Targeting β-thalassaemia
Patients with disorders of the blood protein haemoglobin often depend on lifelong blood transfusions. That could change, given the success of gene therapy in a patient with one such disorder.
- Derek A. Persons
-
News |
Gene-therapy hope for β-thalassaemia patients
A defective haemoglobin gene has been successfully replaced with a healthy copy.
- Joseph Milton
-
Article |
Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia
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 |
ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C
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