Causality and Chance in Cancer and in Other Clonal Diseases

NCI’s Center for Cancer Research (CCR) Grand Rounds Dr. Lucio Luzzatto received his M.D. from the University of Genova and then went on to do a fellowship in hematology at the University of Pavia and receive his Ph.D. in biochemistry from the Ministry of Education in Rome. The leitmotiv of his research has been to understand, in depth, blood diseases with the ultimate purpose to improve their management. In the area of G6PD he did extensive studies in population and biochemical genetics, and in the early eighties cloned the G6PD gene. He took part in solving the 3D structure of human G6PD, and thus eventually he and his colleagues were able to work out the pathophysiology of G6PD deficiency at the molecular level. They did the first field studies and the first studies on the mechanism whereby G6PD deficiency protects from malaria. In research on paroxysmal nocturnal hemoglobinuria (PNH) he first proved that this is a clonal disorder. Subsequently he and his colleagues have introduced the concept of conditional clonal selection and over the years have provided extensive supporting evidence for this model: in essence, we have found that the existence of CD1d-restricted GPI-specific T cells may be the key not only to the pathogenesis of PNH, but also of aplastic anemia in a substantial proportion of cases. In the meantime, he was the senior author of the paper that led to licensing eculizumab, a complement-blocking agent that has become the first PNH-specific medicine. PNH m...
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