Etiological Mechanisms in Childhood Acute Lymphoblastic Leukemia

Greaves, Melvyn F.; Li, Chan; Ford, Anthony M.; Pegram, Susan; Wiedemann, Leanne M.

doi:10.1007/978-1-4615-3898-1_1

Cited by 152 publications

(219 citation statements)

References 79 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…Incidence is higher among more affluent populations, both internationally and within countries, and the peak of incidence in early childhood is also more marked in more affluent countries (Parkin et al, 1998). These patterns are consistent with the hypothesis that precursor B-cell ALL (the most frequent type of childhood ALL, diagnosed mainly between the ages of 1 and 5 years) results from at least two mutations, with the second one being more likely to occur in children in whom delayed exposure to infection led to increased immunological stress (Greaves, 1988).…”

supporting

confidence: 88%

Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward

et al. 2008

View full text Add to dashboard Cite

In this population-based study of acute lymphoblastic leukaemia (ALL) diagnosed among children aged under 15 years in England and Wales during 1986 -1995, we analysed incidence at census ward level in relation to a range of variables from the 1991 census, which could be relevant to theories of infectious aetiology. 'Population-mixing' measures, used as surrogates for quantity and diversity of infections entering the community, were calculated from census data on the origins and destinations of migrants in the year before the census. Incidence at ages 1 -4 years tended independently to be higher in rural wards, to increase with the diversity of origin wards from which in-migrants had moved during the year before the census, and to be lower in the most deprived areas as categorised by the Carstairs index. This last association was much weaker when urban/rural status and in-migrants' diversity were allowed for. There was no evidence of association with population mixing or deprivation for ALL diagnosed at ages 0 or 5 -14 years. The apparent specificity to the young childhood age group suggests that these associations are particularly marked for precursor B-cell ALL, with the disease more likely to occur when delayed exposure to infection leads to increased immunological stress, as predicted by Greaves. The association with diversity of incomers, especially in rural areas, is also consistent with the higher incidence of leukaemia predicted by Kinlen, where population mixing results in below average herd immunity to an infectious agent.

show abstract

supporting

confidence: 88%

Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Greaves' hypothesis adds the importance of timing of the infection. Delayed exposure to common infections increases the pool of preleukaemic cells, while early exposure to common infections may protect children from ALL by contributing to a more normal maturation of the immune system (Greaves, 1988(Greaves, , 1997Greaves and Alexander, 1993). The age-specific incidence peak between 2 and 6 years of age characteristic to ALL in the general population has been described for children with DS as well, providing epidemiological support for an environmental contributor to the aetiology of leukaemia in children with DS and supporting Greaves' hypothesis (Robison et al, 1984;Fong and Brodeur, 1987;Greaves, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Despite this evidence, it is estimated that only 1% of children with DS will ever develop the disease (Taub, 2001). Host genetic susceptibility and environmental exposures likely work together to give rise to leukaemia (Greaves, 1988). For children with DS, trisomy 21 may confer increased genetic susceptibility and represent the first step in a complex multistep pathway to leukemogenesis (Scholl et al, 1982;Ross, 1999).…”

mentioning

confidence: 99%

“…Greaves proposed that childhood acute lymphoblastic leukaemia (ALL), a variant comprising the majority of childhood leukaemia, develops as the result of at least two independent and sequential genetic mutations (Greaves et al, 1985;Greaves, 1988). The first mutation occurs during the expansion of B-cell precursors in utero, giving rise to a population of preleukaemic clone cells (Greaves, 1988;Greaves et al, 2003); the second mutation occurs in a mutant clone during postnatal proliferation of B cells.…”

mentioning

confidence: 99%

“…The first mutation occurs during the expansion of B-cell precursors in utero, giving rise to a population of preleukaemic clone cells (Greaves, 1988;Greaves et al, 2003); the second mutation occurs in a mutant clone during postnatal proliferation of B cells. Greaves hypothesised that exposure to common infections in early childhood may protect the child against ALL by contributing to normal maturation of the immune system, whereas children whose exposure is delayed will be at comparatively higher risk (Greaves, 1988(Greaves, , 1997Greaves and Alexander, 1993). Some studies have supported the possible role of delayed infection in the aetiology of childhood leukaemia (van Steensel-Moll et al, 1986;McKinney et al, 1999;Schuz et al, 1999;Neglia et al, 2000).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group

et al. 2004

View full text Add to dashboard Cite

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N ¼ 173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR) ¼ 0.55, 95% confidence interval (CI) (0.33 -0.92); OR ¼ 0.53, 95% CI (0.29 -0.97); and OR ¼ 0.59, 95% CI (0.28 -1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.

show abstract

Evaluation of the Association Between Congenital Cytomegalovirus Infection and Pediatric Acute Lymphoblastic Leukemia

et al. 2023

View full text Add to dashboard Cite

ImportanceAcute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer, and a leading cause of death in children. Understanding the causes of pediatric ALL is necessary to enable early detection and prevention; congenital cytomegalovirus (cCMV) has recently been identified as a potential moderate-to-strong factor associated with risk for ALL.ObjectiveTo compare the prevalence of cCMV infection between ALL cases and matched controls.Design, Setting, and ParticipantsIn this population-based case-control study of ALL cases and matched controls, cases consisted of children aged 0 to 14 years between 1987 and 2014 with an ALL diagnosis identified through the Michigan Cancer Surveillance Program and born in Michigan on or after October 1, 1987. Cancer-free controls were identified by the Michigan BioTrust for Health and matched on age, sex, and mother’s race and ethnicity. Data were analyzed from November to May 2022.ExposurescCMV infection measured by quantitative polymerase chain reaction in newborn dried blood spots.Main Outcomes and MeasuresALL diagnosed in children aged 0 to 14 years.ResultsA total of 1189 ALL cases and 4756 matched controls were included in the study. Bloodspots were collected from participants at birth, and 3425 (57.6%) participants were male. cCMV was detected in 6 ALL cases (0.5%) and 21 controls (0.4%). There was no difference in the odds of cCMV infection comparing ALL cases with controls (odds ratio, 1.30; 95% CI, 0.52-3.24). Immunophenotype was available for 536 cases (45.1%) and cytogenetic data for 127 (27%). When stratified by subtype characteristics, hyperdiploid ALL (74 cases) was associated with 6.26 times greater odds of cCMV infection compared with unmatched controls (95% CI, 1.44-27.19).Conclusions and RelevanceIn this case-control study of cCMV and pediatric ALL, cCMV was associated with increased risk of hyperdiploid ALL. These findings encourage continued research.

show abstract

Etiological Mechanisms in Childhood Acute Lymphoblastic Leukemia

Cited by 152 publications

References 79 publications

Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward

Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group

Evaluation of the Association Between Congenital Cytomegalovirus Infection and Pediatric Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About