Lymphoblastic Leukaemia in Siamese Twins: Evidence for Identity

Pombo‐de‐Oliveira, Maria S.; Seed, F.E.R. Awad el; Foroni, L.; Matutes, E; Morilla, Ricardo; Luzzatto, Lucio; Catovsky, Daniel

doi:10.1016/s0140-6736(86)90616-1

Cited by 16 publications

(3 citation statements)

References 7 publications

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“…A significant finding in this direction was provided by a short report that a pair of infant twin's leukemic cells appeared to share the same or similar IGH gene rearrangement, that is, same-sized restriction fragment in a Southern blot. 51 This evidence was limited, however, by the fact that only one restriction enzyme was used, and, furthermore, the twins were conjoined with shared vascular connections after birth as well as before. IGH and TCR can provide supportive evidence for a common clonal origin of twin leukemias (below), but unequivocal evidence comes from the use, as clonal markers, of leukemia fusion genes generated by chromosome translocation.…”

Section: Molecular Evidence For a Monoclonal Prenatal Origin Of Leukmentioning

confidence: 99%

Leukemia in twins: lessons in natural history

Greaves

Maia

Wiemels

et al. 2003

Blood

467

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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Section: Molecular Evidence For a Monoclonal Prenatal Origin Of Leukmentioning

confidence: 99%

Leukemia in twins: lessons in natural history

Greaves

Maia

Wiemels

et al. 2003

Blood

467

397

View full text Add to dashboard Cite

show abstract

“…A number of studies of concordant leukemia have provided evidence to support the sharing of a leukemia initiating clone from one twin to the other (reviewed in 37) An identical DNA rearrangement to the immunoglobulin heavy chain was seen to be shared by B-cell lineage ALL cells from a pair of infant Siamese twin boys who were separated 42 days after birth and both diagnosed with ALL 7 months later. The investigators concluded for twins diagnosed in the first 1–2 years of life with leukemia that a single neoplastic transformation had occurred in utero , rather than there was a strong genetic susceptibility ( Pombode de Oliveira et al, 1986 ). Cytogenetic studies in 1998 showed that the leukemia cells from pediatric monozygotic twins with concordant AML had identical clones by virtue of the shared karyotype +8, inv16, and +21.…”

Section: At Least Two “Hits” Are Needed For Leukemiamentioning

confidence: 99%

Lessons to cancer from studies of leukemia and hematopoiesis

Brown

2022

Front. Cell Dev. Biol.

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The starting point to describing the origin and nature of any cancer must be knowledge about how the normal counterpart tissue develops. New principles to the nature of hematopoietic stem cells have arisen in recent years. In particular, hematopoietic stem cells can “choose” a cell lineage directly from a spectrum of the end-cell options, and are, therefore, a heterogeneous population of lineage affiliated/biased cells. These cells remain versatile because the developmental trajectories of hematopoietic stem and progenitor cells are broad. From studies of human acute myeloid leukemia, leukemia is also a hierarchy of maturing or partially maturing cells that are sustained by leukemia stem cells at the apex. This cellular hierarchy model has been extended to a wide variety of human solid tumors, by the identification of cancer stem cells, and is termed the cancer stem cell model. At least, two genomic insults are needed for cancer, as seen from studies of human childhood acute lymphoblastic leukemia. There are signature mutations for some leukemia’s and some relate to a transcription factor that guides the cell lineage of developing hematopoietic stem/progenitor cells. Similarly, some oncogenes restrict the fate of leukemia stem cells and their offspring to a single maturation pathway. In this case, a loss of intrinsic stem cell versatility seems to be a property of leukemia stem cells. To provide more effective cures for leukemia, there is the need to find ways to eliminate leukemia stem cells.

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“…La posibilidad de que el gemelo de un paciente leucémico desarrolle leucemia se encuentra cercana al 25% (Zuelzer y Cox 1969), habiéndose también identificado un mismo rearreglo genético (inmunoglobulina de cadena pesada) en las células leucémicas de gemelos siameses con leucemia linfocítica aguda (Pombo de Oliveira et al 1986). En 1993 se identificó el arreglo genético MLL, que involucra la translocación t(11;19)(q23;p13), en tres pares de gemelos afectados con LLA tipo T, cuyas características fenotípicas incluían CD2 + , CD3 + , CD7 + (Ford et al 1993).…”

Section: Etiologíaunclassified

Historia e investigación de la leucemia en Costa Rica

Bonilla

2014

RBT

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History of leukemia research in Costa Rica. A review of leukemia worldwide is discussed, focusing on etiology, diagnosis and treatment. The history of research of this type of cancer in Costa Rica is presented through the first hospital diagnosis, the arrival of clinical and laboratory hematologists, the establishment of specialized laboratories, the local hematology teaching programs and the voluntary associations that help patients with leukemia. A brief review of Costa Rican publications in this area and the future of this problem in our country is also shown.

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Lymphoblastic Leukaemia in Siamese Twins: Evidence for Identity

Cited by 16 publications

References 7 publications

Leukemia in twins: lessons in natural history

Leukemia in twins: lessons in natural history

Lessons to cancer from studies of leukemia and hematopoiesis

Historia e investigación de la leucemia en Costa Rica

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