Dr Carolina Vincente-Dueñas (Institute of Biomedical Research of Salamanca, Spain) presented the pre-clinical data [1], in which her lab tested the hypothesis of whether the gut microbiome may serve as an integration hub for environmental signals that modulate the risk of developing B-cell acute lymphoblastic leukaemia (B-ALL), by using a murine model of human B-ALL (Pax5+/- mice).
Pax5+/- mice were raised in either a normal environment or an infection-free environment. The host-gut microbiome of Pax5+/- mice was compared with wildtype mice in both environments. Previous studies have shown that a normal environment increased the incidence of B-ALL in these mice. Furthermore, to determine the contribution of intestinal microbiota to B-ALL development, the gut microbiome was depleted in Pax5+/- and wildtype mice by treating them with an antibiotic cocktail added to their drinking water for a period of 8 weeks. The mice were followed up for 2 years for their gut microbiome and leukaemia development.
The researchers observed that microbiome disturbance by antibiotic treatment early in life was sufficient to induce leukaemia in predisposed mice (48%) even in the absence of an infective environment. In the presence of infectious stimuli, antibiotic treatment increased B-ALL incidence in predisposed mice from 22% to 63%. Microbiome analysis of faecal samples over 2 years found that genetic predisposition to B-ALL associated with a distinct gut microbiome, with a 96.8% prediction rate.
In conclusion, microbiome profiles provide a biomarker that might be used to identify predisposed carriers at risk to develop leukaemia. Furthermore, this study identified microbiome deprivation via antibiotic treatment as a risk factor for leukaemia development. By modulating the microbiome early in life, the risk to develop leukaemia may be reduced in predisposed individuals.
- Vicente-Dueñas C, et al. An intact gut microbiome protects genetically predisposed mice against leukemia. EHA25 Virtual, 11-21 June 2020, Abstract S100.
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Table of Contents: EHA 2020
Featured articles
Myeloid
VIALE-A: newly diagnosed chemo-ineligible AML
DEC10-VEN superior to intensive chemotherapy in high-risk AML
Magrolimab plus azacitidine: good ORR in MDS/AML
Asciminib monotherapy in Ph+ CML: major molecular responses
CML TKI interruption: Swedish registry results
Patients with lower-risk MDS benefit from imetelstat
Better outcomes adding enasidenib to azacitidine in mIDH2-AML
Lymphoid
PET-stratification can omit radiotherapy in early-stage unfavourable Hodgkin lymphoma
Pembrolizumab improves PFS for relapsed/refractory Hodgkin lymphoma
Promising first-in-human trial of epcoritamab in B-NHL
Two trials: acalabrutinib in CLL
Zanubrutinib versus ibrutinib in Waldenström macroglobulinaemia
Deep responses in R/R CLL with venetoclax monotherapy
MRD assessment post-CAR-T predicts ALL allo-HSCT bridging
Plasma Cell Dyscrasias
Daratumumab for light-chain amyloidosis
Isatuximab triplet improves PFS in R/R MM
Initial results from CAR-T cell therapy in MM: KarMMa
Graft-Versus-Host Disease
GRAVITAS-301: improved complete aGVDH response
Ruxolitinib improves steroid-refractory aGVHD across subtypes
Benign Haematology
Paroxysmal nocturnal haemoglobinuria treatment with pegcetacoplan
Mitapivat, a pyruvate kinase-R activator, in SCD is safe with early efficacy results
SCD LentiGlobin gene therapy: new data on VOC and ACS
Paediatric Haematology
Venetoclax + navitoclax promising for R/R ALL or LL
Nivolumab/brentuximab vedotin in R/R HL: good CMR rates
Bench-to-Bedside Science from the Presidential Symposium
Microbiome predicts B-ALL predisposition
Netrin-1 regulates haematopoietic stem cells
Unrecognised role of iron in neutrophil differentiation
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