92 research outputs found
The Role of the Bone Marrow Immune Niche in Preventing Relapse in Adult B-ALL Following Reduced Intensity Conditioning Allogeneic-HSCT
No full textReduced intensity-conditioning (RIC) allogeneic haematopoietic stem cell transplants (alloHSCT) improved event-free survival for patients > 40 years old, as established by the UKALL14 (NCT01085617) trial for patients with B-cell acute lymphoblastic leukaemia (B-ALL). Persistence or reappearance of minimal residual disease is a strong predictor of relapse after RIC alloHSCT in ALL and is associated with ineffective graft-versus-leukaemia (GVL) responses by donor T cells. In this thesis, I sought to characterise differences in the bone marrow (BM) immune cell composition from adult patients with B-ALL who underwent RIC alloHSCT with or without subsequent relapse.
I first identified using mass cytometry, and confirmed using single RNA-sequencing (scRNA-seq), an enrichment in early CD4+ T cell subsets in the BM T cell compartments of patients in remission who later relapsed (CR→Rel) compared to patients who remained in long term remission (CR→CR), post-alloHSCT. However, low sample sizes meant that conclusions lacked statistical power. Furthermore, I also identified an inflammatory myeloid signature using bulk RNA-sequencing, which was further characterised in scRNA-seq in patients who later relapsed, which potentially represented a functional pro-inflammatory immature neutrophil population. Cell-cell interactome analysis predicted increased pro-inflammatory signalling pathways in CR→Rel compared to CR→CR, further suggesting a chronically inflamed BM prior to relapse post-alloHSCT. Investigation of the BM at B-ALL diagnosis identified a similar myeloid signature in patients who eventually relapsed. Further interrogation of this signature in a 150-patient UKALL14 validation cohort identified a significant correlation of the myeloid signature with EFS at diagnosis, however this was not an independent predictor of outcome when adjusted for age.
In summary, my thesis identified BM immune signatures potentially associated with future relapse after RIC alloHSCT for B-ALL, and my data may suggest that a myeloid signature is enriched in both the diagnostic and post-alloHSCT samples of patients destined to relapse, which could be supported by its correlation with age and EFS in a large diagnostic cohort
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A yeast model of Bloom's syndrome
No full textSIGLEAvailable from British Library Document Supply Centre-DSC:DXN021831 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Correction to: Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party (Bone Marrow Transplantation, (2021), 56, 3, (605-613), 10.1038/s41409-020-01069-w)
No full textThe Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party, written by Johannes Schetelig, Patrice Chevallier, Michel van Gelder, Jennifer Hoek, Olivier Hermine, Ronjon Chakraverty, Paul Browne, Noel Milpied, Michele Malagola, Gerard Socié, Julio Delgado, Eric Deconinck, Ghandi Damaj, Sebastian Maury, Dietrich Beelen, Stéphanie Nguyen Quoc, Paneesha Shankara, Arne Brecht, Jiri Mayer, Mathilde Hunault-Berger, Jörg Bittenbring, Catherine Thieblemont, Stéphane Lepretre, Henning Baldauf, Liesbeth C. de Wreede, Olivier Tournilhac, Ibrahim Yakoub-Agha, Nicolaus Kröger, Peter Dreger was originally published Online First without Open Access. After publication in volume 56, issue 3, page 605–613 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0. Open access funding enabled and organized by Projekt DEAL
The effect of the bone marrow microenvironment in B acute lymphoblastic leukaemia upon anti-leukaemia T cells
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The road to refractory graft-versus-host disease is paved with good intentions
No full textRefractory acute graft-versus-host disease (GVHD) occurs when the immune injury exceeds the capacity of injured tissues to regenerate and repair. While glucocorticoids have been used for decades to treat GVHD, Arnhold, Chang, and colleagues in this issue of the JCI question whether this approach can in fact be counterproductive. Using in vivo experimental models of GVHD and in vitro intestinal organoids, the study authors show that glucocorticoid exposure directly impeded small intestinal epithelial proliferation and survival, thus preventing the resolution of injury. These findings suggest that future treatment approaches for acute GVHD should include measures to reduce immune reactivity as well as interventions to actively promote tissue resilience
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