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Identical Cytogenetic Clones and Clonal Evolution in Pediatric Monozygotic Twins With Acute Myeloid Leukemia: Presymptomatic Disease Detection by Interphase Fluorescence In Situ Hybridization and Review of the Literature

Purpose Observation of identical acquired genetic changes in infant monozygotic (MZG) twins with acute leukemia has provided strong evidence for in utero twin-twin transfusion as the cause of concordance. Documentation of similar phenomenon in older MZG twins offers insight into the latency period for leukemia and may provide the opportunity for presymptomatic disease detection in one twin. Design The literature describing leukemia in MZG twins is reviewed and the results of classical and molecular cytogenetic studies of one pair of MZG twins at 3 and 4 years with acute non-lymphocytic leukemia-FAB type Ml are reported. Results The twins studied had cytogenetically identical neo-plastic clones with identical clonal evolution. Retrospective fluorescence in situ hybridization studies demonstrated the presence of the abnormal clone in the asymptomatic twin at the time of bone marrow transplant of the first twin. Conclusions These observations support in utero twin-twin transfer as the origin of leukemic clones in pediatric and infant leukemia, demonstrate that clonal evolution of a leukemic clone may occur years before onset of overt disease, and indicate that knowledge of acquired genetic change(s) in one twin may provide markers to assess disease in the asymptomatic twin.