Pre-natal, Clonal Origin of Acute Lymphoblastic Leukaemia in Triplets

Zuna, Jan; Mužíková, Kateřina; Ford, Anthony M.; Maia, Ana-Teresa; Krejčí, Ondřej; Toušovská, Kateřina; Oravkinova, Irina; Greaves, Mel; Trka, Jan

doi:10.1080/1042819031000123393

Cited by 13 publications

(8 citation statements)

References 16 publications

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“…Our data suggest that the risk of ALL may be affected by postnatal events, such as number, timing, and, possibly, type of common infections. However, these results are not in contradiction with the hypothesis that some ALL arise in the fetal period, as supported by molecular studies (19,27,52,53) and previous results from this Database (54).…”

Section: Discussionsupporting

confidence: 29%

Number of Siblings and the Risk of Lymphoma, Leukemia, and Myeloma by Histopathology

Altieri

Castro

Bermejo

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Epidemiologic evidence indicates that several markers of exposure to childhood infections are inversely associated with the risk of childhood leukemia and lymphomas. We used the Swedish Family-Cancer Database to assess the effects of number of siblings on the risk of nonHodgkin's (n = 7,007) and Hodgkin's lymphomas (n = 3,115), leukemias (n = 7,650), and multiple myeloma (n = 1,492) by histopathology. Poisson regression models included terms for age, sex, family history, period, and socioeconomic index. Having four or more siblings compared with none was associated with an excess risk of childhood acute lymphoblastic leukemia [ALL; rate ratio (RR), 2.11; P trend = 0.001], acute monocytic leukemia (RR, 2.51; P trend = 0.002), and multiple myeloma (RR, 1.34; P trend = 0.006). Having three or more older siblings compared with none decreased the risk of acute monocytic leukemia (RR, 0.35; P trend = 0.001) and childhood ALL (RR, 0.69; P trend = 0.01). The risk of Hodgkin's lymphoma for five or more older siblings compared with none was 0.41 (P trend = 0.003). Acute myeloid leukemia, chronic lymphocytic leukemia, and other lymphoproliferative malignancies were not associated with number of siblings. In conclusion, we found an excess risk of childhood ALL and acute monocytic leukemia in large families. However, for ALL, acute monocytic leukemia, and Hodgkin's lymphoma, younger siblings were strongly protected compared with older siblings. The remarkable protective effect of number of older siblings on acute monocytic leukemia is a novel finding of potential interest. Possible interpretations of our findings in the context of a putative infectious etiology are discussed. (Cancer Epidemiol Biomarkers Prev 2006; 15(7):1281 -6)

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Section: Discussionsupporting

confidence: 29%

Number of Siblings and the Risk of Lymphoma, Leukemia, and Myeloma by Histopathology

Altieri

Castro

Bermejo

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…No TEL-AML gene was present in these patients, but their leukemic cells shared clonotypic IGH sequences. 74 These data suggest that both monozygosity and placental status may be critical for risk of concordant leukemia. All the patients in the LRF series ( Figure 7) with known placental status (17 of 19) had a single placenta.…”

Section: Triplets With Allmentioning

confidence: 93%

Leukemia in twins: lessons in natural history

Greaves

Maia

Wiemels

et al. 2003

Blood

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457

397

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Identical infant twins with concordant leukemia were first described in 1882, and since that time many such pairs of infants and older children have been described. It has long been recognized that this situation offers a unique opportunity to identify aspects of the developmental timing, natural history, and molecular genetics of pediatric leukemia in general. We reviewed both the older literature and more recent molecular biologic studies that have uncovered the basis of concordance of leukemia. Molecular markers of clonality, including unique, genomic fusion gene sequences, have provided unequivocal evidence that twin pairs of leukemia have a common clonal origin. The only plausible basis for this, first suggested more than 40 years ago, is that following initiation of leukemia in one twin fetus, clonal progeny spread to the co-twin via vascular anastomoses within a single, monochorionic placenta. This explanation has been endorsed by the identification of clonotypic gene fusion sequences in archived neonatal blood spots of individuals who subsequently developed leukemia. These analyses of twin leukemias have thrown considerable light on the natural history of disease.They reveal a frequent prenatal origin and an early or initiating role for chromosome translocations. Further, they provide evidence for a variable and often protracted latency and the need, in childhood acute lymphoblastic leukemia (ALL)/acute myeloblastic leukemia (AML), for further postnatal exposures and/or genetic events to produce clinical disease. We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms. IntroductionAround 3 to 4 per 1000 live births produce a clone of 2 genetically identical twins. These twins are monozygotic, being derived from a single fertilized ovum followed by splitting of the early embryo. In contrast, fraternal or nonidentical twins are simultaneously derived from independent, fertilized ova and have the same genetic diversity as non-twinned siblings. The common genetic heritage of monozygotic twins is instantly recognizable in their striking similarity of appearance, and, principally for this reason, they have been singled out in almost all human cultures, historical and contemporary, as deserving of special attention. This unique status is reflected in a rich mythology, literature, and art. 1,2 In some respects, this interest has been relatively trivial, focusing, as did Shakespeare, on the comic potential of mistaken identity. But twins also raise more fundamental philosophical and ethical issues. They challenge our precepts of identity, individuality, and fate. Recently, their "natural" origins have been used, in our view erroneously, to legitimize the prospect of human reproductive cloning. Their common inheritance also raises questions of importance to medicine and, in particular, provides an opportunity to explore vulnerability to disease. Not surprisingly, therefore, twins have been much used, and occasionally abused, in biomedical research.In 1875, Fran...

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“…Studies on monozygotic twins/triplets with acute leukemia (Ford et al, 1993;Zuna et al, 2003) and retrospective analysis of neonatal blood spots (Guthrie cards) (Gale et al, 1997) revealed that acute leukemias are initiated prenatally also in a substantial number of older pediatric patients, often by formation of a leukemogenic fusion gene (e.g., ETV6/RUNX1 (TEL/AML1) or RUNX1/ RUNX1T1 (AML1/ETO)) (Ford et al, 1993;Ford et al, 1998;Wiemels et al, 2002). Prenatal initiation of leukemia with clinical onset delayed typically by several years clearly demonstrates the need for an additional, post-natal hit(s) in the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal origin

Zuna

Žaliová

Mužíková

et al. 2010

Genes Chromosomes & Cancer

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The ETV6/ABL1 (TEL/ABL) fusion gene is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1-positive hematological malignancy have been published, diagnosed with chronic myeloid leukemia, other types of chronic myeloproliferative neoplasm, acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This study reports three new cases (aged 8 months, 5 years, and 33 years) of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed ALL patients (335 children and 57 adults). A thorough review of the literature and an analysis of all published data, including the three new cases, suggest poor prognosis of ETV6/ABL1-positive acute leukemias. The course of the disease in the two pediatric patients is characterized by minimal residual disease monitoring, using quantification of both the ETV6/ABL1 transcript and immunoreceptor gene rearrangements. Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1-positive disease. Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally.

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Pre-natal, Clonal Origin of Acute Lymphoblastic Leukaemia in Triplets

Cited by 13 publications

References 16 publications

Number of Siblings and the Risk of Lymphoma, Leukemia, and Myeloma by Histopathology

Number of Siblings and the Risk of Lymphoma, Leukemia, and Myeloma by Histopathology

Leukemia in twins: lessons in natural history

Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal origin

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