Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation
Konradin F. MüskensNienke WieringaMaaike G. J. M. van BergenJoëll E. BenseBrigit M. te PasAnne P. J. de PagterArjan C. LankesterMarc BieringsDonna NeubergSaskia HaitjemaLeontien C.M. KremerGerwin HulsStefan NierkensJoop H. JansenCaroline A. LindemansAniek O. de GraafMirjam E. Belderbos
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In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.01-0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (odds ratio: 1.07, p<0.001) and the HCT procedure (odds ratio: 2.53, p=0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (VAF >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of post-transplant CH and its impact on future cardiovascular disease, second malignancies and overall survival.Developmental Biology
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Les recentes modifications de la politique d'immigration en Australie ont accru la selection des immigrants (criteres d'utilite economique et sociale). Pres de 20 % de la population australienne ne parle pas aujourd'hui l'anglais comme premiere langue. Dans la milieu scolaire, cette proportion passe de 30 a 90 %. L'A. evalue les consequences a court terme et a long terme des modifications de la politique de l'immigration sur le systeme scolaire
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Colony-stimulating factor
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Summary Haematopoiesis is a self‐renewing and multi‐directional differentiation process of haematopoietic stem cells (HSCs), which is modulated very precisely by the haematopoietic microenvironment in bone marrow. Our previous study has demonstrated that oestrogen‐deficiency leads to haematopoiesis dysfunction which manifests as a decrease in haematopoietic tissues and an increase in adipose tissues in bone marrow. However, the mechanism involved in the oestrogen‐deficiency effects on haematopoiesis dysfunction is not completely understood. In this study, we established an oestrogen‐deficiency rat model by ovariectomy (OVX group). Haematopoiesis was evaluated at the 12th, 16th, 20th, 24th and 28th weeks after operation in the OVX group and its control (Sham group) by pathological examination; the number and function of HSCs were evaluated by flow cytometry analysis and colony‐forming assay respectively. Haematopoietic growth factors levels including granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF), stem cell factor (SCF) and interleukin‐3 (IL‐3) were examined by ELISA kits at different time points. We found that in the OVX group, haematopoiesis dysfunction in bone marrow was observed ( P < 0.05) from the 12th week when compared with the Sham group, and extramedullary haematopoiesis began to appear in the liver and spleen from the 16th week. The number of HSCs and colony‐forming units‐granulocyte/macrophage (CFUs‐GM) in bone marrow was reduced significantly ( P < 0.05) from the 20th and 16th week respectively. Furthermore, GM‐CSF, SCF and IL‐3 in the OVX group decreased significantly ( P < 0.05) since the 12th, 16th and 24th week respectively. Taken together, these results suggested that oestrogen is required for normal haematopoiesis. Oestrogen‐deficiency inducing haematopoiesis dysfunction may be via reduction in HSCs and haematopoietic growth factors at a late stage.
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