Can we prevent childhood Leukaemia?

Greaves, Mel; Cazzaniga, Valeria; Ford, Anthony M.

doi:10.1038/s41375-021-01211-7

Cited by 26 publications

(30 citation statements)

References 79 publications

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“…However, microbiome manipulation has been hypothesized as an innovative approach for leukemia prevention. The idea is that oral administration of benign symbiotics could mimic the protective impact of natural infections during infancy, thus educating the immune system and lowering the possibility to develop the disease in genetically predisposed children [4,138].…”

Section: Discussionmentioning

confidence: 99%

The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia

Dander

Palmi

D’Amico

et al. 2021

IJMS

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Genetic lesions predisposing to pediatric B-cell acute lymphoblastic leukemia (B-ALL) arise in utero, generating a clinically silent pre-leukemic phase. We here reviewed the role of the surrounding bone marrow (BM) microenvironment in the persistence and transformation of pre-leukemic clones into fully leukemic cells. In this context, inflammation has been highlighted as a crucial microenvironmental stimulus able to promote genetic instability, leading to the disease manifestation. Moreover, we focused on the cross-talk between the bulk of leukemic cells with the surrounding microenvironment, which creates a “corrupted” BM malignant niche, unfavorable for healthy hematopoietic precursors. In detail, several cell subsets, including stromal, endothelial cells, osteoblasts and immune cells, composing the peculiar leukemic niche, can actively interact with B-ALL blasts. Through deregulated molecular pathways they are able to influence leukemia development, survival, chemoresistance, migratory and invasive properties. The concept that the pre-leukemic and leukemic cell survival and evolution are strictly dependent both on genetic lesions and on the external signals coming from the microenvironment paves the way to a new idea of dual targeting therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia

Dander

Palmi

D’Amico

et al. 2021

IJMS

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“…This may further affect leukemia development and might even be used as a diagnostic tool in the future. Furthermore, based on epidemiological data, the current hypothesis of infection-triggered leukemia of the most common ALL subtypes (ETV6-RUNX1 and high-hyperdiploid chromosomes) during early childhood implies that a lack of microbial exposure in infancy can promote the emergence of this disease [ 11 ]. In 2018, stool samples of 42 pediatric patients at different timepoints of therapy were analyzed [ 12 ].…”

Section: Current Status Of Microbiome Analysis In Pediatric Allmentioning

confidence: 99%

The Microbiome in Childhood Acute Lymphoblastic Leukemia

Oldenburg

Rüchel

Gössling

2021

Cancers

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For almost 30 years, the term “holobiont” has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.

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“…Data of incidences of childhood ALL by geospace, sex, and age are needed to optimize diagnosis, therapy, research efforts, and perhaps consider prevention efforts. 16 , 17 …”

Section: Epidemiology and Current Outcome Of Childhood Leukaemia In Chinamentioning

confidence: 99%

Toward the Cure of Acute Lymphoblastic Leukemia in Children in China

Chen

Zhang

Gale

et al. 2021

JCO Global Oncology

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This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.

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Can we prevent childhood Leukaemia?

Cited by 26 publications

References 79 publications

The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia

The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia

The Microbiome in Childhood Acute Lymphoblastic Leukemia

Toward the Cure of Acute Lymphoblastic Leukemia in Children in China

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