Origins of chromosome translocations in childhood leukaemia

Greaves, Mel; Wiemels, Joe

doi:10.1038/nrc1164

Cited by 637 publications

(536 citation statements)

References 127 publications

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“…These genetic events are mostly initiated in utero as substantially evidenced by studies of twins with leukemia, retrospective analysis of neonatal blood spots and cord blood screening. 1 The chromosomal translocation t(2;11)(q31;p15) results in the NUP98-HOXD13 (ND13) gene fusion which was first identified in a patient with therapy-related AML. 2 Albeit rare, it is a recurrent event in de novo AML 3 and has also been reported in infant AML.…”

mentioning

confidence: 99%

Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia

et al. 2011

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mentioning

confidence: 99%

Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia

et al. 2011

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“…For this reason the genetic instability has been postulated to be one of the hallmarks of cancer (16). Genetic alterations in ALL (Table 3) include structural or numerical chromosome changes such as translocations or hyperdiploidy (17), deletions and amplifications (15,18).…”

Section: Genetic Aberrationsmentioning

confidence: 99%

“…Some genetic alterations affect only one of these pathways, whereas others act on more than one (2) (17,18) . However, the detection of chromosomal translocations in healthy donors and experiments in transgenic mice indicate that a single chromosomal translocation is not enough to induce leukemia, depending on the translocation investigated.…”

Section: Cell Types Involvedmentioning

confidence: 99%

“…However, the detection of chromosomal translocations in healthy donors and experiments in transgenic mice indicate that a single chromosomal translocation is not enough to induce leukemia, depending on the translocation investigated. Therefore, Greaves postulated a two-step model for childhood leukemia with chromosomal translocations as initiating hit (17). Since the central question in this work is the presence of the fusion genes in MSC from precursor B-ALL patients, the contribution of the BCP-ALL fusion genes to leukemia transformation will be discussed in more detail.…”

Section: Cell Types Involvedmentioning

confidence: 99%

“…The BCR-ABL fusion proteins exhibit increased tyrosine kinase activity that alters signaling pathways that control the proliferation, survival and self-renewal capacity. The BCR-ABL1 fusion gene generates a benign or chronic myeloproliferative clonal expansion in both transgenic mice and adult patients (17). INTRODUCTION 14 the ALL-BFM (Berlin-Frankfurt-Münster) /Co-ALL-07-03 study protocols for initial ALL (31,32) or ALL-REZ-BFM study protocol for relapsed ALL (33)(34)(35) treatment protocol is given in Figure 3.…”

Section: Bcr-abl1 Fusion Genementioning

confidence: 99%

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Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

et al. 2010

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Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark

Fang

et al. 2023

JAMA Netw Open

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ImportanceMaternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies.ObjectiveTo evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study.Design, Setting, and ParticipantsThis population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021.ExposuresMaternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry.Main Outcomes and MeasuresThe primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding.ResultsThis study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers.Conclusions and RelevanceIn this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

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Origins of chromosome translocations in childhood leukaemia

Cited by 637 publications

References 127 publications

Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia

Backtracking to birth of the NUP98-HOXD13 gene fusion in an infant acute myeloid leukemia

Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark

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