A5000049478- Hemoglobinopathies and Related Disorders
- Hematopoietic Stem Cell Transplantation
- Prenatal Screening and Diagnostics
- Blood groups and transfusion
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Cancer-related gene regulation
- Parvovirus B19 Infection Studies
- Chronic Myeloid Leukemia Treatments
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Mesenchymal stem cell research
- Polyomavirus and related diseases
- Ethics and Legal Issues in Pediatric Healthcare
- Bone and Joint Diseases
- Iron Metabolism and Disorders
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Mycobacterium research and diagnosis
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Peptidase Inhibition and Analysis
Imperial College Healthcare NHS Trust
2015-2025
Imperial College London
2015-2025
St. Mary’s Hospital
2008-2025
St Mary's Hospital
2014-2024
St. Mary's Hospital
2015-2024
Hammersmith Hospital
2001-2024
St Mary's Hospital
2010-2024
Cornell University
2021-2024
University College London
2005-2024
Magna Graecia University
2024
Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem progenitor cells obtained from healthy donors, CRISPR-Cas9 targeting the erythroid-specific enhancer. Approximately 80% alleles at this locus were modified, no evidence off-target...
Dyskeratosis congenita (DC) and related syndromes are inherited, life-threatening bone marrow (BM) failure disorders, approximately 40% of cases currently uncharacterized at the genetic level. Here, using whole exome sequencing (WES), we have identified biallelic mutations in gene encoding poly(A)-specific ribonuclease (PARN) 3 families with individuals exhibiting severe DC. PARN is an extensively characterized exonuclease deadenylation activity that controls mRNA stability part therefore...
BackgroundExagamglogene autotemcel (exa-cel) is a nonviral cell therapy designed to reactivate fetal hemoglobin synthesis through ex vivo clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing of the erythroid-specific enhancer region BCL11A in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).MethodsWe conducted an open-label, single-group, phase 3 study exa-cel patients 12 35 years age with transfusion-dependent β-thalassemia β0/β0, β0/β0-like,...
Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable curing these diseases. Allo-HCT has been also shown be curative in benign disorders such as aplastic anemia, sickle disease, and thalassemia, among others. Recently, the American Society for Transplantation Cellular Therapy (ASTCT) published standardized definitions recovery, graft rejection, failure, poor function,...
Related human leukocyte antigen (HLA)-haploidentical bone marrow transplantation (BMT) with posttransplant cyclophosphamide may be curative for sickle cell disease. However, graft failure, severe graft-versus-host disease (GVHD), infections, and mortality remain a concern. We evaluated novel conditioning regimen followed by related HLA-haploidentical BMT in adults In phase 2, open-label, single-arm, multicenter study, 54 eligible participants from 19 U.S. centers were enrolled. Of these, 42...
We explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line with a sibling/family (MSD) HSCT (n = 87) or IST horse antithymocyte globulin and ciclosporin 58) second-line post-failed 24). The 2-year overall survival 96 ± 4% 91 3% MSD (P 0·30) 94 0·68) 74 9% post-IST...
Highlights•Multicenter learning collaborative model of haploidentical bone marrow transplantation (BMT) for sickle cell disease (SCD).•Using BMT as curative therapy SCD increases the donor pool.•Haploidentical with post-transplantation cyclophosphamide (PTCy) plus thiotepa engraftment in SCD.•Event-free survival and overall are improved following haplo-BMT PTCy thiotepa.Graphical abstractComparison contemporary approaches to hematopoietic transplant severe disease. MRD-BMT (Matched Related...
Summary Chronic myeloid leukaemia in children and young people is a relatively rare form of that shows increased incidence with age some evidence suggests the molecular basis differs from adults. Significant advances targeted therapy development use tyrosine kinase inhibitors ability to monitor understand prognostic significance minimal residual disease by standardized techniques has shifted management this condition bone marrow transplantation as main therapeutic modality individualized...
ABSTRACT Sickle cell disease (SCD) remains associated with reduced life expectancy and poor quality of despite improvements observed in the last decades mostly related to comprehensive care, use hydroxycarbamide, screening identify patients at risk strokes, implementation safe transfusion protocols. The course is highly variable, making it difficult predict severity response therapy. Allogeneic hematopoietic stem transplantation potentially provides a cure relatively low rate complications,...
First-trimester fetal blood contains a readily expandable population of stem cells, human mesenchymal cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation hfMSCs after transduction with onco-retroviral lentiviral vectors. After either MoMuLV retrovirus or an HIV-1-based vector carrying ss-galactosidase green fluorescent reporter gene, respectively, transgene expression, self-renewal, capabilities were assessed...
Abstract: DC is a multisystem bone marrow failure syndrome exhibiting marked clinical and genetic heterogeneity. X‐linked, autosomal dominant recessive subtypes are recognized. The gene mutated in X‐linked (DKC1) encodes highly conserved nucleolar protein called dyskerin. Dyskerin associates with the H/ACA motif class of small RNAs ribonucleoprotein particles that important guiding conversion uracil to pseudouracil during maturation ribosomal RNA. also TERC, which maintenance telomeres....
BACKGROUND: Hyperhemolysis syndrome (HS) has been well described both in sickle cell disease (SCD) and non‐SCD patients. The pathogenesis remains unclear. possible mechanisms include bystander hemolysis, suppression of erythropoiesis, destruction red cells (RBCs) due to contact lysis via activated macrophages. CASE REPORT: This study reports a child with SCD who presented recurrent episode HS. In the first episode, hemoglobin (Hb) level decreased 4.1 g per dL. He was treated intravenous...
Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy hemoglobin synthesis and halts disease symptoms in patients with sickle thalassemia major. A disease-free survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling is performed young low-risk or treatment-related risk factors. Alternate adults infrequently because of a higher profile. Transplant-specific risks include conditioning regimen-related...
Genotype-phenotype correlations are revealed by bone marrow single-cell RNA sequencing in Diamond-Blackfan anemia.
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after haematopoietic stem cell transplantation from matched unrelated donors (MUD). The role T-cell depletion (TCD) as strategy to prevent GVHD is controversial because the associated increased risk leukaemic relapse, graft failure delayed immune reconstitution. demonstration that donor lymphocyte infusion (DLI) effective salvage therapy if patients relapse for chronic myeloid leukaemia (CML) prompted us...