A causal mechanism for childhood acute lymphoblastic leukaemia.
TLDR
Evidence supporting the model that infections early in life reduce the risk of childhood common B cell precursor acute lymphoblastic leukaemia (BCP-ALL) development is described, given this evidence, paediatric BCP-ALL may be a preventable cancer.Abstract:
In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)–runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations. Risk is further modified by inherited genetics, chance and, probably, diet. Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. Childhood ALL may be a preventable cancer.read more
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Cancer health disparities in racial/ethnic minorities in the United States
Valentina A. Zavala,Paige M. Bracci,John M. Carethers,Luis G. Carvajal-Carmona,Nicole B. Coggins,Marcia Cruz-Correa,Melissa Davis,Adam J. de Smith,Julie Dutil,Jane C. Figueiredo,Rena K. Fox,Kristi D. Graves,Scarlett Lin Gomez,Andrea S. Llera,Susan L. Neuhausen,Lisa A. Newman,Tung T. Nguyen,Julie R. Palmer,Nynikka R. Palmer,Eliseo J. Pérez-Stable,Sorbarikor Piawah,Erik J. Rodriquez,María Carolina Sanabria-Salas,Stephanie L. Schmit,Silvia J. Serrano-Gomez,Mariana C. Stern,Jeffrey N. Weitzel,Jun J. Yang,Jovanny Zabaleta,Elad Ziv,Laura Fejerman +30 more
TL;DR: To eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.
Journal ArticleDOI
Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia.
David T. Teachey,Ching-Hon Pui +1 more
TL;DR: Novel treatments under investigation might narrow the gap in survival between T- cell ALL and B-cell ALL, although novel treatment options for T-cell All are limited.
Journal ArticleDOI
Urban-associated diseases: Candidate diseases, environmental risk factors, and a path forward.
Emily J. Flies,Suzanne Mavoa,Graeme R. Zosky,Evangeline Mantzioris,Craig R. Williams,Rajaraman Eri,Barry W. Brook,Jessie C. Buettel +7 more
TL;DR: Identifying urban-associated diseases and their drivers will allow us to prepare for the urban-disease burden of the future and create healthy cities that mitigate that disease burden.
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Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs
Sorcha O’Byrne,Natalina Elliott,Siobhan Rice,Gemma Buck,Nicholas Fordham,Catherine Garnett,Laura Godfrey,Nicholas T. Crump,Gary Wright,Sarah Inglott,Peng Hua,Peng Hua,Bethan Psaila,Benjamin J. Povinelli,David J. H. F. Knapp,Antonio Agraz-Doblas,Antonio Agraz-Doblas,Clara Bueno,Ignacio Varela,Phillip R. Bennett,Hashem Koohy,Suzanne M. Watt,Anastasios Karadimitris,Adam J. Mead,Adam J. Mead,P Ancliff,Paresh Vyas,Paresh Vyas,Pablo Menendez,Thomas A. Milne,Thomas A. Milne,Irene Roberts,Irene Roberts,Anindita Roy +33 more
TL;DR: Fetal PreProB- upstream of ProB-progenitors are identified as the first B-lymphoid restricted progenitor in human fetal life, and it is suggested that this fetal-restricted committed B-pro genitor might provide a permissive cellular context for prenatal B- Progenitor leukemia initiation.
Journal ArticleDOI
The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy, asthma, allergy and obesity in childhood.
TL;DR: The use of antibiotics prenatally, during pregnancy, or neonatally may have adverse effects on the neonatal gut microbiome, and adversely affect the development of the infant immune system as mentioned in this paper.
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Journal ArticleDOI
Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns
Maria Gloria Dominguez-Bello,Elizabeth K. Costello,Elizabeth K. Costello,Monica Contreras,Magda Magris,Glida Hidalgo,Noah Fierer,Rob Knight +7 more
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Journal ArticleDOI
Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes
Siddhartha Jaiswal,Pierre Fontanillas,Jason Flannick,Jason Flannick,Alisa K. Manning,Peter V. Grauman,Brenton G. Mar,Brenton G. Mar,R. Coleman Lindsley,Craig H. Mermel,Noël P. Burtt,Alejandro Chavez,John M. Higgins,Vladislav Moltchanov,Vladislav Moltchanov,Frank C. Kuo,Michael J. Kluk,Brian E. Henderson,Leena Kinnunen,Heikki A. Koistinen,Heikki A. Koistinen,Claes Ladenvall,Gad Getz,Adolfo Correa,Benjamin F. Banahan,Stacey Gabriel,Stacey Gabriel,Sekar Kathiresan,Heather M. Stringham,Mark I. McCarthy,Michael Boehnke,Jaakko Tuomilehto,Jaakko Tuomilehto,Jaakko Tuomilehto,Christopher A. Haiman,Leif Groop,Gil Atzmon,James G. Wilson,Donna Neuberg,David Altshuler,Benjamin L. Ebert +40 more
TL;DR: Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease.
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Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Nicholas Arpaia,Clarissa Campbell,Xiying Fan,Stanislav Dikiy,Joris van der Veeken,Paul deRoos,Hui Liu,Justin R. Cross,Klaus Pfeffer,Paul J. Coffer,Alexander Y. Rudensky +10 more
TL;DR: The results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
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