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. In contrast, fraternal or nonidentical twins are simultaneously derived from independent, fertilized ova and have the same genetic diversity as non-twinned siblings.
These twins are monozygotic, being derived from a single fertilized ovum followed by splitting of the early embryo. 2003 102:2321-2333)Īround 3 to live births produce a clone of 2 genetically identical twins. We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms. 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. They reveal a frequent prenatal origin and an early or initiating role for chromosome translocations. These analyses of twin leukemias have thrown considerable light on the natural history of disease. This explanation has been endorsed by the identification of clonotypic gene fusion sequences in archived neonatal blood spots of individuals who subsequently developed leukemia. 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. Molecular markers of clonality, including unique, genomic fusion gene sequences, have provided unequivocal evidence that twin pairs of leukemia have a common clonal origin. We reviewed both the older literature and more recent molecular biologic studies that have uncovered the basis of concordance of leukemia. 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. 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.
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