Sarah Inglott
Great Ormond Street Hospital
GeneHaematopoiesisInternal medicineOncologyAntigenFetusProgenitor cellImmunologyT cellCyclophosphamideImmunotherapyB cellLeukemiaJuvenile myelomonocytic leukemiaFludarabineMyeloidBone marrowCytokine release syndromeStem cellPopulationLymphoblastic LeukemiaTransplantationChimeric antigen receptorCancer researchMedicineBiology
Publications 30
#1Neha Jain (GOSH: Great Ormond Street Hospital)H-Index: 13
#2Shaista Sattar (GOSH: Great Ormond Street Hospital)
Last. Tanzina Chowdhury (GOSH: Great Ormond Street Hospital)H-Index: 11
view all 13 authors...
Background: Bone marrow involvement is an important aspect of determining staging of disease and treatment for childhood neuroblastoma. Current standard of care relies on microscopic examination of bone marrow trephine biopsies and aspirates respectively, to define involvement. Flow cytometric analysis of disaggregated tumour cells, when using a panel of neuroblastoma specific markers, allows for potentially less subjective determination of the presence of tumour cells. null Methods: A retrospec...
#1Virginia Turati (UCL: University College London)H-Index: 6
#2José Afonso Guerra-Assunção (UCL: University College London)H-Index: 22
Last. Gillian May (UCL: University College London)H-Index: 8
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Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We therefore investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic ver...
2 CitationsSource
#1Jack Bartram (GOSH: Great Ormond Street Hospital)H-Index: 15
#2Milena Balasch‐Carulla (GOSH: Great Ormond Street Hospital)
Last. Vesna Pavasovic (GOSH: Great Ormond Street Hospital)H-Index: 3
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1 CitationsSource
#1E Louka (University of Oxford)H-Index: 2
#2Benjamin J. Povinelli (University of Oxford)H-Index: 8
Last. Adam J. Mead (University of Oxford)H-Index: 34
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Juvenile myelomonocytic leukemia (JMML) is a poor-prognosis childhood leukemia usually caused by RAS-pathway mutations. The cellular hierarchy in JMML is poorly characterized, including the identity of leukemia stem cells (LSCs). FACS and single-cell RNA sequencing reveal marked heterogeneity of JMML hematopoietic stem/progenitor cells (HSPCs), including an aberrant Lin-CD34+CD38-CD90+CD45RA+ population. Single-cell HSPC index-sorting and clonogenic assays show that (1) all somatic mutations can...
8 CitationsSource
#1Laura Godfrey (University of Oxford)H-Index: 7
#2Nicholas T. Crump (University of Oxford)H-Index: 8
Last. Thomas A. Milne (University of Oxford)H-Index: 36
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MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine-79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1, which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glyco...
12 CitationsSource
Summary Background Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children an...
29 CitationsSource
#1Karin StraathofH-Index: 23
#2Barry FlutterH-Index: 4
Last. T GileadiH-Index: 1
view all 42 authors...
#1Karin Straathof (Great Ormond Street Hospital for Children NHS Foundation Trust)H-Index: 1
#2Barry Flutter (Great Ormond Street Hospital for Children NHS Foundation Trust)H-Index: 1
Last. John Anderson (Great Ormond Street Hospital for Children NHS Foundation Trust)H-Index: 48
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The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractor...
11 CitationsSource
#1Siobhan Rice (University of Oxford)H-Index: 4
#2Thomas R. Jackson (University of Oxford)H-Index: 2
Last. Anindita Roy (University of Oxford)H-Index: 15
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ABSTRACT Although 90% of children with acute lymphoblastic leukemia (ALL) are now cured1, the prognosis of infant-ALL (diagnosis within the first year of life) remains dismal2. Infant-ALL is usually caused by a single genetic hit that arises in utero: rearrangement of the MLL/KMT2A gene (MLL-r). This is sufficient to give rise to a uniquely aggressive and treatment-refractory leukemia compared to older children with the same MLL-r3–5. The reasons for disparate outcomes in patients of different a...
2 CitationsSource
#1Sarah Leong (UCLH: University College Hospital)H-Index: 1
#2Sarah Inglott (GOSH: Great Ormond Street Hospital)H-Index: 8
Last. David O'Connor (UCL: University College London)H-Index: 16
view all 19 authors...
2 CitationsSource